Management of Immunity Alteration-Induced Chronic Pain During the Coronavirus Disease-2019 (COVID-19) Pandemic

Abstract

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was identified at the end of 2019, has become a widespread, global public health crisis, raising many concerns (Khan et al., 2020). According to the newest data from the World Health Organization (WHO), global SARS-CoV-2 infection cases have reached 18.6 million, with the reported deaths of more than 700,000 individuals (WHO, 2020). Coronaviruses are enveloped, positive-stranded RNA viruses, with an average diameter of 100 nm. The genome length of most coronaviruses ranges from 26 to 32 kb. Coronaviruses can infect various vertebrate species, including bats, dogs, and humans (Fan et al., 2019; Sit et al., 2020). Since the start of the Twenty one century, humans have encountered coronavirus outbreaks three times: severe acute respiratory syndrome-associated coronavirus (SARS-CoV-1), in 2003 (de Wit et al., 2016), Middle East respiratory syndrome-related coronavirus (MERS-CoV), in 2008 (Hemida et al., 2020), and SARS-CoV-2, in 2019 (Wu F. et al., 2020). Genetic comparisons have indicated 79.5% similarity between SARS-CoV-2 and SARS-CoV, and the similarity is up to 96% between SARS-CoV-2 and a coronavirus strain isolated from bats (Zhou et al., 2020). According to the structural and genome-wide association studies, SARS-CoV-2 can more easily infect and replicate in host cells than other coronaviruses (Gussow et al., 2020; Yan et al., 2020). SARS-CoV-2 infections are responsible for the ongoing, global COVID-19 pandemic, which has a fatality rate between 2 and 4% (Weiss and Murdoch, 2020). SARS-CoV-2 infections result in major impacts on the human respiratory system (Rothan and Byrareddy, 2020), with fever, mild cough, pneumonia, and dyspnoea (Singhal, 2020). COVID-19 patients also experience various neurological symptoms, such as headache, epilepsy, disturbed consciousness (Mao et al., 2020; Wu Y. et al., 2020), smell, vision and taste loss, neuralgia (Jin et al., 2020; Mao et al., 2020), and acute neurological disorders, such as stroke and seizure (Jin et al., 2020) in COVID-19 patients. It has been reported that SARS-CoV-2 infection affected the central and peripheral nervous system manifesting as dysosmia, visual disturbances, and neuralgia after (Mao et al., 2020). Abdelnour et al. has reported a case of SARS-CoV-2 infection manifesting as peripheral neuropathy (Abdelnour et al., 2020). This evidence demonstrates that SARS-CoV-2 can cause serious malfunction and damage to both the central and peripheral nervous systems. It has been reported that SARS-CoV-2 infections in elderly and weak individuals cause more severe syndromes, such as acute respiratory distress syndrome (ARDS) and acute lung injury (ALI), which are associated with lung malfunction and death (Matuschak and Lechner, 2010). Patients with chronic obstructive pulmonary disease (COPD) and smoking history have also been reported to experience worse progression and outcomes when diagnosed with COVID-19 (Zhao et al., 2020). COVID-19 in cancer patients has a 36% lethality, and worse prognosis has been observed among older individuals (Stroppa et al., 2020). Human immunodeficiency virus (HIV)-positive patients may be more vulnerable to COVID-19 due to their immune-compromised status. A recent clinical observation reported that COVID-19 results in a death rate of approximately 9% among patients living with HIV (Harter et al., 2020). Besides, some patients treated with opioids could be more susceptible to SARS-CoV-2 infections because treatments with morphine and fentanyl have been reported to be the most immunosuppressive (Mellon and Bayer, 1998; Shavit et al., 2004). Opioids act on the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system, further suppressing the immune system (Mellon and Bayer, 1998; Shavit et al., 2004; Plein and Rittner, 2018). These studies suggest that hypo-immune individuals might have higher risks and worse outcomes associated with COVID-19. On the other hand, the possibility of SARS-CoV-2 infection in hyper-immune individuals is also worldwide discussed because of their immunological background and therapies. It has been reported that hyper-immunity individuals have received treatment with immunosuppressive or modulatory agents; these approaches may increase the possibility of SARS-CoV-2 infection (Cai et al., 2020). Therefore, individuals with altered immunity (hypo-immune & hyper-immune) may require additional attention to prevent the infection of SARS-CoV-2 during the COVID-19 outbreak. It is known that the induction of a cytokine storm is the basic cause of pathogenic inflammation in COVID-19 (Jose and Manuel, 2020; Mehta et al., 2020). Cytokine storm is an acute hyperinflammatory response responsible for critical illness in many conditions, including viral infections, cancer, sepsis, and multi-organ failure (Bhaskar et al., 2020). The elevation of cytokines in the blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients (Bhaskar et al., 2020). Laboratory results have shown that dysregulation in the immune system has occurred in COVID-19 patients. SARS-CoV-2 infection increases the plasmatic secretion of interleukin 1β, interferon-γ, interferon-γ-induced proteins, monocyte chemoattractant protein-1, IL-4, and IL-10 (Vinciguerra et al., 2020). Moreover, it has been reported that SARS-CoV-2 infection induces the up-regulation of a series of interferon-stimulated genes, indicative of immune and interferon responses to the virus (Blanco-Melo et al., 2020). These results demonstrated that SARS-CoV-2 infection-induced immune alteration in COVID-19 patients. The SARS-CoV-2 infection causes systemic inflammation and dysregulation of immunity, resulting in various delayed neurological complications. Both central and peripheral nervous systems have been reported to be involved in the immune-mediated...