Anales de la RANM

284 A N A L E S R A N M R E V I S T A F U N D A D A E N 1 8 7 9 SARS-COV-2 INFECTION IN A PATIENT WITH PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA Pablo Estival An RANM · Año 2020 · número 137 (03) · páginas 281 a 285 SARS-CoV2 infection presents a variable clinical course, while most subjects with SARS-CoV-2 develop mild to moderate symptoms, others contract profound seemingly unchecked inflam- matory responses, leading to acute lung injury and hypoxemic respiratory failure, the most common cause of death (3). The foundation to these diverse clinical manifestations is still unknown, and many of the usable scientific hypotheses came from previous studies from MERS and SARS coronavirus outbreaks. Available evidence suggests that SARS-CoV-2 disease is characterized by an excessive inflam- matory response, implying an activation of innate immune pathways, with a cytokine storm syndrome development, resembling secondary hemophago- cytic lymphohistiocytosis (sHLH) (4). Likewise, there is also pathological activation of thrombin. Multiple thrombotic episodes had been observed, from thrombotic microangiopathy and dissemi- nate intravascular coagulation, to thromboembo- lism (5). The complement system is a vital element of innate immune response. It works by recogni- zing molecular patterns present in pathogens and autologous apoptotic cell debris. Its final target is to promote the opsonization and direct lysis of these cells. There is accumulating evidence suggesting that the overactivation of the complement system caused by coronavirus may have a major role in the pathogenesis of ARDS (6). Furthermore, as studies suggest that lung damage caused by SARS-CoV-2 alone is not responsible for all pathological changes associated with typical ARDS. Significant deposits of complement's MAC, C4d and mannose binding lectin (MBL)-associated protease, as well as co-localization of SARS-CoV-2 spike glycoprotein were shown in skin and lung microvasculatures of SARS-CoV-2 patients. These findings suggest that in some critical patients, SARS-CoV-2 may involve catastrophic thrombotic microvascular injury, mediated by activation of the complement alterna- tive pathway and lectin pathway. Therefore, available evidence supports the important role of the complement system in the development of pulmonary damage associated to SARS-CoV-2. Diurno et al reported their experience with four patients admitted in ICU with SARS-CoV-2 severe pneumonia, who were treated with eculizumab. All of them successfully recovered. None of these patients carried a diagnosis of PNH (7). Giudice et al recently reported a study with seven patients treated with the novel combination of ruxolitinib and eculizumab compared to ten patients with the best available therapy. Patients treated with the combination showed significant improve- ments in respiratory symptoms and radiogra- phic pulmonary lesions and decrease in circula- ting D-dimer levels compared to the best available therapy group (8). Figure 2. Evolution of the patient’s lower-right lobar infiltrate in 3 con- secutive PA and lateral radiogra- phies. A: 08th April 2020. B: 13th April 2020. C: 27th April 2020. DISCUSSION A B C A B C