Persisting Shadows: Unraveling the Impact of Long COVID-19 on Respiratory, Cardiovascular, and Nervous Systems
Abstract
:1. Introduction
2. Health Implications Related to Long COVID
2.1. Effect of Long COVID on the Respiratory System
2.2. Effect of Long COVID on the Cardiovascular System
2.3. Effect of Long COVID on the Nervous System
3. Potential Mechanisms Resulting in Long COVID-19
- (i)
- Direct Damage of the organs/system via the ACE2 receptor: ACE2 has a pivotal role in developing cardiac, brain, and pulmonary complications, as already mentioned [43,93,116]. The Renin–Angiotensin–Aldosterone System (RAAS) is a signaling pathway that acts as a homeostatic regulator of vascular function. Τhe Ang II depending on the receptor type, can have different effects: the classic effects (increased oxidative stress, inflammation, fibrosis, and vasoconstriction) and the opposite effects [117]. The ACE2 is a homolog of the ACE [118] and has a vital role in the RAAS. ACE2 regulates the action of ACE by decreasing the amount of Ang II and increasing the amount of Ang-(1–7). Furthermore, the ACE2, beyond participating in the RASS system, is the gateway for the entry of SARS-CoV-2 [77]. The virus competes with Ang II, and its binding blocks the ACE2 activity. This decreases the enzyme activity at the membrane, resulting in an imbalance of ACE/ACE2 and, consequently, the RASS. This imbalance will lead to an increase in the abnormal activation of the ACE/Ang II/AT1 receptor axis and thus an increase in the Ang II vasoconstriction and a decrease in the Ang vasodilation (1-7) [119].
- (ii)
- Indirect damage through the immune system: Myocardial injury in COVID-19 can occur indirectly through an overactive inflammatory response, often referred to as a ‘cytokine storm’ [73,74]. This hyperinflammatory state poses a significant risk not only to the cardiovascular system but also to the brain and respiratory tissues [48]. Typically, COVID-19 patients exhibit an imbalanced immune profile: an overzealous innate immune response coupled with a diminished adaptive immune response. This manifests as a reduction in various immune cells—lymphocytes, cytotoxic and helper T cells, B cells, and NK cells—particularly in severe cases [120]. The cytokine storm triggered by SARS-CoV-2 infection results in the rampant release of proinflammatory cytokines, creating a disequilibrium between proinflammatory and anti-inflammatory processes [49,121,122]. Elevated levels of interleukin-6 (IL-6) during the acute phase have prompted investigations into its role in long-term COVID-19 sequelae [123,124,125], suggesting that persistent inflammation could underlie the pathophysiology of Long COVID. Further research is essential to elucidate these mechanisms and identify effective treatments to improve the long-term outlook for patients.
- (iii)
- Therapeutic implications: Antiretroviral therapies, including azithromycin and tocilizumab, have been associated with electrophysiological alterations and potential interactions with cardiovascular drugs, warranting cautious use and monitoring [74]. Concurrently, the role of RAAS inhibitors in modifying ACE2 levels is under scrutiny, given their potential dual impact on the disease process [126]. Moreover, severe COVID-19 cases requiring prolonged mechanical ventilation can suffer from heightened intrapulmonary pressure, leading to or exacerbating pulmonary fibrosis [127]. Additionally, the high concentrations of oxygen used to treat critically ill patients can generate free radicals, damaging pulmonary epithelium and contributing to oxidative stress. This stress not only perpetuates the inflammatory state but also may activate fibrogenic pathways, further complicating recovery [58].
- (iv)
- Sociopsychological factors: The pervasive impact of COVID-19 extends beyond the physical to the psychological, with social isolation, the stress of a novel and potentially fatal virus, and the anxiety surrounding transmission and stigma all contributing to long-term psychiatric conditions. Post-acute sequelae may include PTSD, depression, anxiety, and obsessive–compulsive symptoms [82,128]. The enforced solitude, disruption of normal work routines, and financial strains—compounded by the overarching threat of a global health emergency—can engender loneliness, anxiety, and significant behavioral shifts [129,130]. Consequently, the occurrence of anxiety disorders, depressive states, and cognitive deficits is thought to be multifaceted in origin, encompassing a spectrum of physical, functional, and sociopsychological contributors [92].
Risk Factors Contributing to the Development of Long COVID
4. Potential Therapies for Long COVID-19 Syndrome
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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n | Follow Up 1 | Main Findings/Symptoms | Ref |
---|---|---|---|
478 | 4 months |
| [34] |
76 | 3 months |
| [37] |
200 | 42 days |
| [36] |
119 | 61 days |
| [38] |
41 | 7 months |
| [39] |
59 | 30 days |
| [40] |
n | Follow Up 1 | Main Findings/Symptoms | Ref |
---|---|---|---|
100 | 71 days |
| [65] |
26 | 47 days |
| [66] |
384 | 54 days | In the study population:
| [67] |
148 | 68 days |
| [68] |
346 | 109 days |
| [69] |
180 | ≥12 weeks | In the study population:
| [47] |
n | Follow Up 1 | Main Findings/Symptoms | Ref |
---|---|---|---|
1276 | 6 months–1 Year |
| [82] |
2433 | 1 year |
| [89] |
165 | 6 months |
| [90] |
120 | 110 Days |
| [84] |
100 (32 in ICU, 62 in the hospital ward) | 48 Days |
| [91] |
236, 379 | 6 Months |
| [92] |
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Sideratou, C.-M.; Papaneophytou, C. Persisting Shadows: Unraveling the Impact of Long COVID-19 on Respiratory, Cardiovascular, and Nervous Systems. Infect. Dis. Rep. 2023, 15, 806-830. https://doi.org/10.3390/idr15060072
Sideratou C-M, Papaneophytou C. Persisting Shadows: Unraveling the Impact of Long COVID-19 on Respiratory, Cardiovascular, and Nervous Systems. Infectious Disease Reports. 2023; 15(6):806-830. https://doi.org/10.3390/idr15060072
Chicago/Turabian StyleSideratou, Christina-Michailia, and Christos Papaneophytou. 2023. "Persisting Shadows: Unraveling the Impact of Long COVID-19 on Respiratory, Cardiovascular, and Nervous Systems" Infectious Disease Reports 15, no. 6: 806-830. https://doi.org/10.3390/idr15060072