To the Editor,
Coronavirus disease 2019 (COVID-19) is a respiratory and systemic illness that may
progress to severe hypoxemia needing some form of ventilatory support in as many as
15–20% of suspected and confirmed cases [1]. In outbreak regions, the surge in critically
ill patients has placed significant strain on intensive care units (ICUs), with volume
demands that overwhelm current capacity [1]. There is a compelling need to identify
clinical predictors of severe COVID-19 to enable risk stratification and optimize
resource allocation.
Chronic Obstructive Pulmonary Disease (COPD) is associated with increased risk of
morbidity and mortality in community-acquired pneumonia (CAP) [2]. Alterations in
local/systemic inflammatory response, impaired host immunity, microbiome imbalance,
persistent mucus production, structural damage, and use of inhaled corticosteroids
have been hypothesized to contribute to such risk [3]. With respect to COVID-19, levels
of angiotensin converting enzyme 2 (ACE2), the reported host receptor of the virus
responsible of COVID-19 (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2),
have been observed to be increased in patients with COPD [4,5]. However, early individual
COVID-19 studies have not consistently reported a significantly higher rate of severe
disease in COPD patients [6,7]. In this article, we analyze if COPD may be associated
with increased odds of severe COVID-19 infection.
An electronic search was performed in Medline (PubMed interface), Scopus and Web of
Science, using the keywords “chronic obstructive pulmonary disease” OR “COPD” OR “clinical
characteristics” AND “coronavirus 2019” OR “COVID-19” OR “2019-nCoV” OR “SARS-CoV-2”,
between 2019 and present time (i.e., March 9, 2020). No language restrictions were
applied. The title, abstract and full text of all articles captured with the search
criteria were evaluated, and those reporting the rate of COPD in COVID-19 patients
with a clinically validated definition of severe disease were included in this meta-analysis.
The reference list of all identified studies was also analyzed (forward and backward
citation tracking) to detect additional articles.
The obtained data was pooled into a meta-analysis, with estimation of the odds ratio
(OR) and its 95% confidence interval (95% CI) in patients with or without severe forms
of COVID-19. The statistical analysis was performed using MetaXL, software Version
5.3 (EpiGear International Pty Ltd., Sunrise Beach, Australia). The study was carried
out in accordance with the declaration of Helsinki and with the term of local legislation.
Overall, 87 articles were initially identified based on our electronic and reference
search, which after screening by tile, abstract, and full text, 80 were excluded as
not related to COVID-19 (n = 27), were review articles (n = 7), did not provide relevant
data (n = 28), were editorials (n = 10), did not provide data on severity or comorbidities
(n = 5), compared patients by mortality not severity (n = 2) or compared mild cases
to critical cases (n = 1). Thus, a total number of 7 studies were finally included
in our meta-analysis, totaling 1592 COVID-19 patients, 314 of which (19.7%) had severe
disease [[6], [7], [8], [9], [10], [11], [12]].
The essential characteristics of the included studies are shown in Table 1
, whilst the individual and pooled OR of COPD for predicting severe COVID-19 is presented
in Fig. 1
. Only in a single study was the individual OR found to be a significant predictor
of COPD [8]. However, when the data of the individual studies was pooled, COPD was
found to be significantly associated with severe COVID-19 (OR: 5.69 [95:CI: 2.49–13.00],
I2 = 0.0%, Cochran's Q, p = 0.95). A leave-one-out sensitivity analysis, excluding
the largest study by Guan et al. [8] which accounted for 52.3% of pooled weight, found
no significant differences (OR: 5.88 [95%CI: 1.78–19.50]).
Table 1
Characteristics of included studies.
Table 1
Study
Setting
Sample Size
Outcomes
Severe patients
Non-severe patients
n (%)
Age (yrs)a
Women (%)
n (%)
Age (yrs)a
Women (%)
Guan W et al., 2020
China
1099
Admission to ICU, MV, death
173 (15.7%)
52 (40–65)
42%
926 (84.3%)
45 (34–57)
42%
Huang C et al., 2020
China
41
ICU Care
13 (31.7%)
49 (41–61)
15%
28 (68.3%)
49 (41–58)
32%
Liu W et al., 2020
China
78
Admission to ICU, MV, Death
11 (14.1%)
66 (51–70)
36%
67 (85.9%)
37 (32–41)
52%
Liu Y et al., 2020
China
12
Respiratory Failure, MV
6 (50%)
64 (63–65)
50%
6 (50.0%)
44 (35–55)
17%
Wang D et al., 2020
China
138
Clinical Variables, MV, Death
36 (26.1%)
66 (57–78)
39%
102 (73.9%)
51 (37–62)
48%
Young BE et al., 2020
Singapore
18
Treatment, ICU Care, Death
6 (33.3%)
56 (47–73)
67%
12 (66.6%)
37 (31–56)
42%
Zhang JJ et al., 2020
China
140
Respiratory Distress/Insufficiency
58 (41.4%)
64 (25–87)
43%
82 (58.6%)
52 (26–78)
54%
a
Age data presented as median (IQR). MV – Mechanical Ventilation, ICU – Intensive Care
Unit.
Fig. 1
Forest plot demonstrating association of Chronic Obstructive Pulmonary Disease with
severe COVID-19 disease.
Fig. 1
In conclusion, the results of this concise meta-analysis demonstrate COPD is associated
with a significant, over five-fold increased risk of severe CODID-19 infection. Patients
with a history of COPD should be encouraged adopt more restrictive measures for minimizing
potential exposure to SARS-CoV-2 and contact with suspected or confirmed cases of
COVID-19. Clinicians should also carefully monitor all COPD patients with suspected
infection and, finally, it may be advisable to consider COPD as a variable in future
risk stratification models.
Declaration of competing interest
None declared.