A 47-year-old man was admitted to our ID unit in February 2022 for fever, dyspnea, and confusion. He had a history of mantle cell non-Hodgkin lymphoma, treated with autologous hematopoietic stem-cell transplantation in July 2019, on maintenance therapy with rituximab every 6 months (last administration of rituximab in December 2021). The patient was vaccinated against SARS-CoV-2 with two doses of mRNA vaccine (the last dose in April 2021). In January 2022 he had mild COVID-19 not requiring hospitalization, with spontaneous resolution of symptoms and with consecutive negative molecular NP swabs. At the beginning of February, he developed fever (maximum 39 C), accompanied after 4 days by the onset of dry cough. This event was interpreted as a bacterial lower respiratory tract infection, and the patient was treated at home with empirical oral antibiotic therapy (no corticosteroids were used), without resolution of symptoms. Due to worsening conditions, with spikes of high fever, sweating, persistence of dry cough, and confusion, he was admitted to our ID unit.
Blood tests were performed at hospital admission (Day 0): white blood cell 2,640/mul (range 4,500-9,800), neutrophils 2.130/mul (range 1,800-7,800), creatinine 1.2 mg/dl (range 0.67-1.17), mild elevation of liver enzymes (ALT/AST 50/61 UI/ml, range 0-40, 0-40, respectively), lactate dehydrogenase 444U/L (range 135-225), ferritin 1,972 mcg/L (range 30-400), C reactive protein 89.4 mg/L (range 0-3), Interleukin-6 46.5 ng/L (normal value, n.v., <3.4).
SARS-CoV-2 serology resulted non-reactive: IgG anti Receptor-Binding Domain (RBD) < 1 U/ml < 12 negative), IgG anti Spike 1 (S1) < 1 U/ml (<21 negative), IgG anti Spike 2 (S2) < 1 U/ml (<9 negative), IgG anti Nucleocapsid < 1 U/ml (<23 negative). Rapid antigenic test and molecular test for SARS-CoV-2 performed on NP swabs were negative on Day 1. Computed tomography (CT) scan performed on Day 1 showed extensive bilateral ground-glass opacities with crazy-paving aspects and more consolidated components, greater at lower lobes in subpleural location (Figure 1A).
Given the radiological evidence of pneumonia in a suspected bacterial infection after the recent SARS-CoV2 infection, a bronchoalveolar lavage (BAL) was performed. Empirical antibiotic therapy with ceftobiprole and levofloxacin was started.
On day 7, due to the worsening clinical conditions, with fever up to 40.5 C and need for supplemental oxygen, he underwent a second CT scan, showing the extension of pulmonary opacities at the left basal lobe compared to the previous imaging (Figure 1B). The antibiotic therapy was changed to ceftolozane/tazobactam plus linezolid.
The same day a RT-PCR on BAL resulted positive for SARS-CoV-2, showing no other concomitant bacterial/fungal/viral infections (culture tests for common bacteria - Aspergillus spp. - M. tuberculosis, M. tuberculosis DNA, Pneumocystis jirovecii DNA, serum beta-D-glucan, BAL galactomannan, BAL CMV-DNA, all tested negative). Blood testing for SARS-CoV-2 RNAemia was performed as well on day 7 and resulted positive.
In consideration of worsening bilateral pneumonia in an immunocompromised hematological patient with COVID-19 and no other clear alternative diagnoses for pneumonia, an off-label combination of sotrovimab 500 mg in a single infusion, a seven-day course of IV remdesivir (200 mg of loading dose, 100 mg of maintenance dose) plus a five-day course of oral nirmatrelvir/ritonavir 300 mg/100 mg q12h and intravenous (IV) corticosteroids was then started on day 7. The patient signed the informed consent for off-label treatment.
Sotrovimab was chosen over casirivimab/imdevimab due to the prevalence of variant of concern Omicron BA.1 at that time in Italy, on which the latter has reduced efficacy.
Adjunctive anti-inflammatory treatment (i.e., IL-6 or IL-1 receptor inhibitors) were not deemed necessary considering the presence of SARS-CoV-2 positive RNAemia and the absence of SARS-CoV-2-related inflammatory pattern.
No adverse effects were observed during the course of treatment.
From day 9 the patient remained afebrile, with clinical improvement and consequent reduction in oxygen demand on day 10, until complete weaning to room air on day 13.
On day 12 SARS-CoV-2 RNAemia resulted negative, as well as RT-PCR on NP swab. A follow up PET scan for the non-Hodgkin lymphoma was performed, showing uptake exclusively at the level of the ground-glass pulmonary thickening, suggesting local inflammatory signs of infection and thus ruling out any sign of progression of his hematological disease.
In consideration of the improved conditions and of the reduction of inflammatory parameters, the patient was discharged on day 17.