BAL in suspected COVID-19 non-critically ill patients.
As recently reported by systematic reviews and metanalysis several
retrospective and few prospective observational studies have
investigated the role of BAL in suspected or known
COVID-19.18,19 To the best of our knowledge, all
studies performed in the non-critically ill patients are retrospective.
A summary of BAL findings in non-critically ill patients is reported in
Table 1 and 2. Between January and February 2020 Chinese scientists
reported 5 cases of suspected COVID-19 investigated with BAL showing
positivity for SARS-Cov-2 in all cases.20Subsequently, between March and May 2020, Italian virologists confirmed
a higher positivity in BAL compared to other specimens (15%, 55/367
positive BAL, compared to 8%, 769/9461 positive NP
swabs).21 A small retrospective case series reported a
19% prevalence (3/19 cases) of SARS-Cov-2 infection in BAL performed in
patients with negative NP swab.22 During the first
COVID-19 wave (March-April 2020), De Clercq et al conducted a
retrospective monocentre study in Belgium aimed to evaluate the
feasibility of their local diagnostic protocol that included BAL in
patients’ diagnostic workup.23 They performed 27 BAL
in non-critically ill patients with HCRT changes suspected for COVID-19
and two negative NP swabs and found 26% (7/27) positive BAL for
SARS-Cov-2. They also identified one coinfection in SARS-Cov-2 positive
(E cloacae) and 63% of other pathogens in negative BAL for SARS-Cov-2
including Mycoplasma pneumoniae, Streptococcus pneumoniae,
Haemophilus influenzae, Pneumocysitis jirovecii , and other
viruses.23 Another retrospective study conducted in
two Belgian centres during the first wave confirmed the utility of BAL
in detecting SARS-Cov-2 in 25% (14/55) of non-critically ill patients
with negative NP swabs.24 The Authors also underlined
the utility of BAL in therapeutic management that was changed after BAL
in 60% of cases (33/55), either because other pathogens were identified
(one coinfection with Serratia marcescens in SARS-Cov-2 positive
cases and 42%, 23/55 of other pathogens in SARS-Cov-2 negative cases
including Mycobacterium tuberculosis, Pneumocystis jirovecii,
Haemophilus, Serratia, Escherichia coli, virus Influenza type A,
Metapneumoviruses, Herpes viruses and Aspergillus fumigatus ) or because
an alternative diagnosis was made (18% of cases, 10/55, including
rheumatoid arthritis, hypersensitivity pneumonitis, cardiogenic oedema,
cryptogenic organizing pneumonia, hepatopulmonary
syndrome).24 During the first COVID-19 wave, Mondoni
et al. carried out in Italy an observational, retrospective, multicentre
cohort study aimed to evaluate the diagnostic yield of bronchoscopy in
patients with two negatives NP swabs and suspected
COVID-19.25 A total 109 adults, 71% males, age 60 (SD
13.6) years were enrolled, 108 bronchoscopies (99%) performed with
flexible scope and 13 with rigid. Two-third of the procedures (N=78)
were performed to confirm a COVID-19 diagnosis, and one-third were
urgent/life-saving procedures. Only 10% of the procedures were carried
out in the ICU setting (8.2% invasive ventilation, 1.8% ECMO). The
diagnostic yield of bronchoscopy to detect SARS-Cov-2 in patients with
previous negative swabs and a clinical and radiological suspicion of
COVID-19 pneumonia was 55.1% (43/78). 1.8% (2/109) patients with both
NP swabs and BAL negative for SARS-Cov-2 showed a late NP swabs
positivity. Coinfections were detected in 4 cases (3,6% of the total):Haemophilus influenzae, Aspergillus fumigatus, Aspergillus spp.
and Candida albicans .25 In the same period
(March-April 2020) Patrucco and coworkers conducted a similar Italian
observational, retrospective, multicentre cohort study including 131
suspected COVID-19 with two negative NP swabs (male 71%, age 65, range
54-74 years) the majority in Internal Medicine ward (63%), 27.5% in
sub-intensive unit and 9% in ICU. SARS-Cov-2 was isolated in 43
(32.8%) BAL.26 Positive patients were younger
compared to the negative ones (56 vs. 67, p=0.004) and showed a higher
HRCT involvement (ground-glass, peripheral, posterior and multilobar
involvement).26 Other microbiological findings were
identified in 26 cases (19.8%) and included Herpesviruses,
Cytomegalovirus, Staphylococcus aureus, Escherichia coli, Klebsiella
pneumoniae, Pseudomonas aeruginosa and fungi . Considering both the
identification of COVID-19 and the detection of other causal agent, BAL
microbiological analysis was considered clinically useful in 67% of
cases.26 Barberi et al in a population of hospitalized
patients for suspected COVID-19, negative NP swabs and mild-moderate
disease severity (PaO2/FiO2 307, range 254-362), confirmed a BAL
positivity of 16% (32/198), 9% (5/54 in patients with negative
HRCT).27 Moreover, BAL detected 12.5% (4/32) of
coinfections in SARS-Cov-2 positive patients and 33% of other
infections in SARS-Cov-2 negative patients. The logistic regression
analysis detected two factors predictive of BAL positivity: fever (OR
1.94 per additional °C, 95% CI 1.13-3.33, p=0.016) and HRCT scan
involvement grade 2 or more (OR 7.36, 95%CI 2.10-25.77,
p=0.002).27 Contrarily to those results, three Italian
single centre observational retrospective studies on BAL conducted in
the same time period (March-May 2020) in suspected COVID-19 with
negative NP swabs (N=81, N=79 and N=28 patients respectively), showed
poor BAL performance in detecting SARS-Cov-2 infection with 3/81
(3.7%), 2/79 (2.5%) and 0/28 positive BAL.28-30 In
those studies BAL negative for SARS-Cov-2 was still useful to identify
other microorganisms (mycobacteria, Pneumocystis, Haemophilus
parainfluenzae, Staphylococcus, Pseudomonas, Streptococcus,
Enterobacterales, Klebsiella, Candida, and other
viruses ).29,30 Two American studies found a 100%
concordance between negative NP swabs and BAL conducted in patients that
were screened for SARS-Cov-2 before an elective bronchoscopy for
suspected diseases other than COVID-19 (obstructive diseases,
interstitial lung disease, lung transplant surveillance
etc).31,32 In the study conducted by Oberg et al, all
but one patient had HRCT non suggestive for COVID-19 (negative HRTC in
58% and indeterminate or atypical in the remaining cases) and none had
clinical-laboratory features of COVID-19.31 This study
suggests that when the clinical-radiological scenario is not suggestive
of COVID-19 and the NP swabs is negative, BAL for COVID-19 is unlikely
to be useful, even during a pandemic peak.
Among these small retrospective studies there is a notable variably in
the reported utility of BAL for the detection of SARS-Cov-2. This
suggests that several factors may influence BAL diagnostic accuracy in
detecting SARS-Cov-2, including the heterogeneity of the populations,
the variability in BAL technique and sample processing. It is important
to mention that BAL diagnostic yield for COVID-19 detection is also
influenced by the epidemiological incidence of the disease and may be
influenced by the viral variant. With the changing epidemiological
scenario and novel omicron variant the BAL diagnostic yield could
significantly change. In Figure 2 we present a paradigmatic case in
which BAL allowed the diagnosis of COVID-19 (Omicron variant),
aspergillosis and transbronchial biopsy detected lung metastasis from
melanoma. Prospective studies conducted in larger and more recent
populations are needed, particularly considering that the clinical
scenario is rapidly changing due to the emergence of the Omicron variant
in the vaccinated population.