Mild clinical manifestations of SARS-CoV-2 related pneumonia in two patients with multiple sclerosis under treatment with ocrelizumab

Case 1: A 36-year-old Caucasian woman was admitted to Tor Vergata Hospital in Rome on March 29^th, 2020, because of 4-day fever with dry cough and coryza. Her husband was previously diagnosed with SARS-CoV-2 infection. Her past medical history was notable for papillary thyroid carcinoma in 2014, HPV infection and diagnosis of highly active relapsing remitting multiple sclerosis (RRMS) in 2018. On March 2019 the patient was started on ocrelizumab (last infusion in September 2019). At hospital admission the Expanded Disability Status Scale (EDSS) was 5,5. SARS-CoV-2 infection was assessed with a RT-PCR on a NPh swab, with the detection of E, N and RdRP gene sequences. The chest CT-scan showed the presence of a single ground-glass area in the subpleural region of the inferior lobe of the left lung (Fig. 1A). Other viral (Influenza, parainfluenza, syncytial respiratory virus, metapneumovirus, adenovirus, rhinovirus) and bacterial (Legionella pneumophila and Streptococcus pneumoniae) infections were excluded. Laboratory findings are represented in Fig. 2. Plaquenil 200 mg twice daily for 10 days and lopinavir/ritonavir 400/100 mg twice daily for 12 days were administered. During hospitalization chest CT-scan was repeated after 8 days from hospitalization (+12 days from symptom onset), showing bilateral ground-glass opacities of the lungs (Fig. 1B). Notably, D-dimers peaked concomitantly with the worsening of lung infiltrates and tended to normalize with the resolution of pneumonia. No oxygen therapy was needed during hospitalization and the patient was discharged in good clinical condition and unremarkable arterial blood gases, on room air. Two negative NPh swabs for SARS-CoV-2 RT-PCR were obtained after 19 days from symptoms onset. IgG and IgM were undetectable up to 27 days from symptom onset. Follow-up chest CT-scan was performed 27 days after symptom onset and showed the complete resolution of lung ground glass opacities (Fig. 1C).

Case 2: A 54-year-old Caucasian man was admitted to Tor Vergata Hospital in Rome on April 4^th, 2020, because of 5-day fever. Before hospital admission, the patient was living in a nursing home, where other cases of COVID-19 have been diagnosed. His past medical history was notable for the diagnosis of secondary progressive multiple sclerosis (PPMS) in 2003. First line treatment was interferon beta 1a (2004-2011), followed by second line treatment with fingolimod (2011-2017). In 2018 the patient experienced a deep venous thrombosis treated with rivaroxaban and placement of an inferior vena cava filter for the prevention of pulmonary embolism. On November 2018 the patient was started on ocrelizumab (last infusion in November 2019). At hospital admission the EDSS was 7. SARS-CoV-2 infection was assessed with a RT-PCR assay on a NPh swab, with the positivity for E, N and RdRP genes of SARS-CoV-2. The chest CT-scan showed the presence of widespread bilateral ground-glass opacities (Fig. 1C). Other viral and bacterial infections were excluded. Laboratory findings are represented in Fig. 2. During hospitalization, interstitial pneumonia was monitored with chest CT-scans performed at 8 and 24 days after hospitalization, showing first the extension of bilateral ground-glass opacities of the lungs and then the complete resolution (Fig. 1D, E). Notably, leukocyte and CD4 absolute counts were reduced at hospital admission, while CRP, D-dimers and fibrinogen peaked concomitantly with the extension of lung infiltrates and normalized with the resolution of pneumonia. No oxygen therapy was necessary during hospitalization and the patient was discharged in good clinical condition and unremarkable peripheral oxygen saturation, on room air, while NPh swab for SARS-CoV-2 RT-PCR was still positive. IgG and IgM were undetectable up to 18 days from symptom onset, while IgG became slightly detectable after 28 days from symptom onset (17,9 AU/ml, cutoff: >15 AU/ml, CLIA DiaSorin^TM)