Neuroinvasion of SARS-CoV-2 may play a role in the breakdown of the respiratory center of the brain.

The recent outbreak of the novel coronavirus, SARS-CoV-2, has emerged to be highly pathogenic in nature. Although lungs are considered as the primary infected organs by SARS-CoV-2, some of the other organs, including the brain, have also been found to be affected. Here, we have discussed how SARS-CoV-2 might infect the brain. The infection of the respiratory center in the brainstem could be hypothesized to be responsible for the respiratory failure in many COVID-19 patients. The virus might gain entry through the olfactory bulb and invade various parts of the brain, including the brainstem. Alternatively, the entry might also occur from peripheral circulation into the central nervous system by compromising the blood-brain barrier. Finally, yet another possible entry route could be its dispersal from the lungs into the vagus nerve via the pulmonary stretch receptors, eventually reaching the brainstem. Therefore, screening neurological symptoms in COVID-19 patients, especially toward the breakdown of the respiratory center in the brainstem, might help us better understand this disease.

Brainstem Dysfunction in SARS-COV-2 Infection can be a Potential Cause of Respiratory Distress.

BACKGROUND: A terrible pandemic, Covid-19, has captivated scientists to investigate if SARS-CoV-2 virus infects the central nervous system (CNS). A crucial question is if acute respiratory distress syndrome (ARDS), the main cause of death in this pandemic, and often refractory to treatments, can be explained by respiratory center dysfunction. OBJECTIVE: To discuss that ARDS can be caused by SARS-CoV-2 infection of the respiratory center in the brainstem. MATERIALS AND METHODS: I reviewed literature about SARS-CoV-2 mechanisms to infect the respiratory center in the brainstem. RESULTS AND CONCLUSIONS: An increasing amount of reports demonstrates that neurotropism is a common feature of coronavirus, which have been found in the brains of patients and experimental models, where the brainstem was severely infested. Recent studies have provided tremendous indication of the incidence of acute respiratory failure due to SARS-CoV-2 infection of the brainstem. SARS-CoV-2 might infect the CNS through the olfactory bulb, spreading from the olfactory nerves to the rhinencephalon, and finally reaching the brainstem. Hence, the virus infection causes respiratory center dysfunctions, leading to ARDS in COVID-19 patients. I conclude that acute ARDS in Covid-19 can be caused by SARS-CoV-2 invasion of brainstem respiratory center, suggesting the needs of more specific and aggressive treatments, with the direct participation of neurologists and neurointensivists.

Computing the Effects of SARS-CoV-2 on Respiration Regulatory Mechanisms in COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been established as a cause of severe alveolar damage and pneumonia in patients with advanced Coronavirus disease (COVID-19). The consolidation of lung parenchyma precipitates the alterations in blood gases in COVID-19 patients that are known to complicate and cause hypoxemic respiratory failure. With SARS-CoV-2 damaging multiple organs in COVID-19, including the central nervous system that regulates the breathing process, it is a daunting task to compute the extent to which the failure of the central regulation of the breathing process contributes to the mortality of COVID-19 affected patients. Emerging data on COVID-19 cases from hospitals and autopsies in the last few months have helped in the understanding of the pathogenesis of respiratory failures in COVID-19. Recent reports have provided overwhelming evidence of the occurrence of acute respiratory failures in COVID-19 due to neurotropism of the brainstem by SARS-CoV-2. In this review, a cascade of events that may follow the alterations in blood gases and possible neurological damage to the respiratory regulation centers in the central nervous system (CNS) in COVID-19 are related to the basic mechanism of respiratory regulation in order to understand the acute respiratory failure reported in this disease. Though a complex metabolic and respiratory dysregulation also occurs with infections caused by SARS-CoV-1 and MERS that are known to contribute toward deaths of the patients in the past, we highlight here the role of systemic dysregulation and the CNS respiratory regulation mechanisms in the causation of mortalities seen in COVID-19. The invasion of the CNS by SARS-CoV-2, as shown recently in areas like the brainstem that control the normal breathing process with nuclei like the pre-Bötzinger complex (pre-BÖTC), may explain why some of the patients with COVID-19, who have been reported to have recovered from pneumonia, could not be weaned from invasive mechanical ventilation and the occurrences of acute respiratory arrests seen in COVID-19. This debate is important for many reasons, one of which is the fact that permanent damage to the medullary respiratory centers by SARS-CoV-2 would not benefit from mechanical ventilators, as is possibly occurring during the management of COVID-19 patients.

Is the Collapse of the Respiratory Center in the Brain Responsible for Respiratory Breakdown in COVID-19 Patients?

Following the identification of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, we are now again facing a global highly pathogenic novel coronavirus (SARS-CoV-2) epidemic. Although the lungs are one of the most critically affected organs, several other organs, including the brain may also get infected. Here, we have highlighted that SARS-CoV-2 might infect the central nervous system (CNS) through the olfactory bulb. From the olfactory bulb, SARS-CoV-2 may target the deeper parts of the brain including the thalamus and brainstem by trans-synaptic transfer described for many other viral diseases. Following this, the virus might infect the respiratory center of brain, which could be accountable for the respiratory breakdown of COVID-19 patients. Therefore, it is important to screen the COVID-19 patients for neurological symptoms as well as possibility of the collapse of the respiratory center in the brainstem should be investigated in depth.