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Acute respiratory distress syndrome during the COVID-19 pandemic: not only SARS-CoV-2

A previously healthy 30-year-old woman developed severe ARDS at the beginning of the COVID-19 pandemic. SARS-CoV-2 infection was suspected, but testing was negative. Mycoplasma pneumoniae was detected by PCR in bronchoalveolar lavage fluid and blood. This case illustrates that M. pneumoniae infection can progress to septicemia and ARDS with severe respiratory failure in young healthy adults.

To the Editor, Severe coronavirus disease 2019 (COVID-19) most commonly manifests as viral pneumonia-induced acute respiratory distress syndrome (ARDS) [1]. At the beginning of the COVID-19 pandemic, a previously healthy 30-year-old woman presented with sore throat, cough, headache and arthralgia for 5 days. She rapidly developed severe multilobar pneumonia with haemolytic anaemia, septic shock and, ultimately, ARDS [2] with severe respiratory failure requiring mechanical ventilation and venovenous extracorporeal membrane oxygenation (vv-ECMO) 8 days after symptom onset (Fig. 1).
The patient did not improve with broad-spectrum antibiotics (including amoxicillin-clavulanate, clarithromycin, piperacillintazobactam and meropenem), but only upon intravenous doxycycline treatment (100 mg twice daily for 14 days). Serological testing was negative for antinuclear antibodies, antineutrophil cytoplasmic antibodies and anti-glomerular basement membrane antibodies. Direct antiglobulin test serology was positive with the detection of cold agglutinins. Human immunodeficiency virus screen was negative. The clinical course was complicated by hypercoagulopathy as a result of disseminated intravascular coagulation, which led to extensive acral necroses requiring debridement.
Mycoplasma pneumoniae ARDS occurs mainly in young adults without known underlying disease [6,7,9]. This is in line with experimental and clinical data suggesting that an 'overreacting' host cell-mediated immune response contributes to M. pneumoniae pulmonary disease [13]. The magnitude of the specific T-cell response has been shown to correlate with the severity of pulmonary infiltrates [8,14]. Mycoplasma pneumoniae produces a community-acquired respiratory distress syndrome (CARDS) toxin, which can trigger cellular inflammation and mediate organ damage [2,12]. Mycoplasma pneumoniae septicaemia in our patient may have triggered massive cell-mediated immune responses resulting in ARDS [12][13][14].
Mycoplasma pneumoniae ARDS manifests after an interval of 1-3 weeks from onset of respiratory symptoms [6,7,9], which coincides with the timing of acquired immunity and further suggests that M. pneumoniae ARDS may represent an immune-mediated complication [6][7][8][9][10]. This hypothesis could also be the explanation for the favourable response to corticosteroid treatment observed in some individuals with M. pneumoniae ARDS [7][8][9].
Our case further highlights that in addition to PCR (in BALF and/ or blood) the measurement of M. pneumoniae-specific ASCs can help to confirm M. pneumoniae aetiology in ARDS. Mycoplasma pneumoniae-specific ASCs are short-lived and associated with clinical disease [5]. We recently demonstrated that M. pneumoniaespecific IgM ASCs measured by ELISpot assay were detectable in children with M. pneumoniae community-acquired pneumonia, but not in M. pneumoniae carriers suffering from community-acquired pneumonia caused by other pathogens or asymptomatic M. pneumoniae carriers [4]. The measurement of specific ASCs in ARDS may be especially useful to determine true M. pneumoniae infection in the case of co-detection of M. pneumoniae and other respiratory pathogens by PCR and/or serology [4,15]. Establishing an early and rapid diagnosis of M. pneumoniae ARDS is essential to stop further disease progression using targeted antimicrobial treatment.

Authors' contributions
PMMS, GRK and WCA contributed to patient care and/or diagnostic work up; PMMS and WCA drafted the manuscript; and all authors critically reviewed the manuscript.