The severity of COVID-19 illness caused by SARS-CoV-2 may extend from asymptomatic infection or mild self-limiting upper respiratory tract illness, to severe pneumonia with respiratory failure, or death.¹ The presence of comorbidities such as diabetes, hypertension, chronic obstructive pulmonary disease (COPD) and malignancies correlate with worsened clinical outcomes of COVID-19;² and indeed, COPD independently enhances susceptibility to COVID-19 infection owing to compromised lung reserves and up-regulated expression of angiotensin-converting enzyme 2 (ACE-2) receptors in the small airways.¹ Additionally, the coexistence of COPD with other systemic diseases may cause disordered pulmonary ventilation, thereby increasing the risk of infection and jeopardising treatment outcomes.³

COPD is characterised by chronic bronchitis and emphysema with ensuing destruction of alveoli structure. Previous studies reported that comorbid COPD correlated with a more serious COVID-19 infection and inflammatory responses, leading to severe illness or death.^3,4 However, the severity of COPD does not influence the clinical outcomes of COVID-19, including the length of hospitalisation, need for intensive care, respiratory failure and death.¹

The impact of the COPD pathophysiology on the clinical course of COVID-19 was recently explored in a retrospective observational study at Wuhan Huoshenshan Hospital, involving 156 COVID-19 patients with and without (age- and sex- matched) pre-existing COPD (n=78 each).⁵ The primary outcome measures were the onset of ICU admission, use of mechanical ventilation, or death during hospitalisation; recorded secondary outcomes were virus clearance, disease progression, disease deterioration, and death. Individualised treatment for COVID-19 consisted of oxygen support, antivirals, secondary infection control, immune-modulators, and multi-organ support; whilst COPD treatment included the use of anti-asthmatics, inhaled corticosteroid, leukotriene receptor antagonist, phosphodiesterase-4 inhibitors, and expectorants, depending on patients’ needs.

The key findings of the study included:⁵

• The incidence of COPD significantly corresponded to older age and male sex (P<0.001), as reported by previous studies.^1,3,4
• COPD was independently correlated with poor clinical outcomes.
  • Patients with pre-existing COPD (in comparison with non-COPD counterparts), presented with significant dyspnoea (59.0% vs 37.2%; P<0.01) and required therapy with expectorants, sedatives, and mechanical ventilation (P<0.05), indicating the existence of acute exacerbations of COPD.
  • Greater proportions of COPD patients showed significantly higher likelihood of developing respiratory failure (19.2% vs 5.1%; P<0.01), a marginally significant likelihood of developing cardiac insufficiency (10.3% vs 2.6%; P=0.050), and increased risk of mortality (HR, 3.875; P=0.065).
• Besides an increase in IL-6 levels (P=0.017), patients with COPD did not experience over-activated inflammatory responses or multiorgan injury (P>0.05).
• COPD patients exhibited longer viral clearance time from the respiratory tract.
  • Although pre-existing COPD did not influence the risk of disease progression (hazard ratio [HR], 1.227; P=0.363), COPD increased the risk of disease deterioration by 139.4% (HR, 2.394; P=0.025) and the risk of unfavourable clinical outcomes by 230.8% (HR, 3.308; P=.013).
• Surprisingly, no significant difference in COVID-19 disease severity was observed between the COPD and non-COPD groups (62.8% vs 61.5%; P=0.868).

The occurrence of dyspnoea in the hospitalised COPD patients was attributed to – (i) the acute phase of COPD itself; and (ii) the synergistic pulmonary over-inflammation and functional collapse exerted by COPD and COVID-19.⁵

Bai Y and colleagues concluded that COPD pathophysiology itself does not account for the over-activated inflammation status seen in severe COVID-19.⁵ However, COPD may independently confer increased risk of unfavourable clinical outcomes by causing dysregulation of the antiviral immune response and subsequent susceptibility to virus-induced exacerbations and respiratory failure.⁵

References

1. Lee SC, et al. Scientific reports 2021;11(1):3735.
2. Guan WJ, et al. Respir 2020;55(6):2001227.
3. He Y, et al. Med Sci Monitor Int Med J Exp Clin Res 2020;26:e927212.
4. Alberca RW, et al. Front Physiol 2020;11:637627.
5. Bai Y, et al. Medicine2020;101(18):e29141.