Patient A was a 72-year-old man who came to Irrua Specialist Teaching Hospital (ISTH) in Irrua, Nigeria, on January 15, 2021, because of reported weakness and poor appetite. He had previously been given artemether/lumefantrine for suspected malaria for 4 consecutive days. However, his symptoms persisted. His medical history included diabetes mellitus type 2 and arterial hypertension. At examination, the patient was in apparent good clinical condition, afebrile, and had normal vital signs and adequate peripheral oxygenation at ambient air.

A molecular test of an oropharyngeal swab specimen for SARS-CoV-2 showed a positive result (reverse transcription PCR [RT-PCR] cycle threshold [Ct] 14.97 for betacoronavirus] and Ct 12.3 for SARS-CoV-2). Oral dexamethasone therapy was initiated, and the patient was referred to domestic quarantine, according to standard local practice. Two days later, the patient came again to the hospital and reported progressive worsening of body weakness; he appeared pale and in a markedly reduced clinical condition.

He had a body temperature of 38.0°C, heart rate 105 bpm, blood pressure 115/75 mm Hg, respiratory rate 24/min, and 95% oxygen saturation in ambient air. Auscultation of the chest and further physical examination showed no abnormalities.

The patient was admitted to the isolation ward and tested for Lassa fever because of persistent fever and worsening condition in a zone to which Lassa fever is endemic. The result was positive (Ct 33.33, by RealStar Lassa Virus RT-PCR Kit; Altona Diagnostics, https://www.altona-diagnostics.com).

During hospitalization, the patient required 2–4 L/min of supplemental oxygen by nasal cannula, received intravenous ribavirin according to the Irrua regimen (3) and continued therapy with dexamethasone (8 mg orally every 8 h). Laboratory diagnosis showed anemia and acute renal failure (Table). An initial treatment with prophylactic low molecular weight heparin was discontinued once Lassa fever was diagnosed to avoid exacerbation of risk for bleeding in viral hemorrhagic fever. The patient had progressive normocytic anemia and received 2 blood transfusions. Stool for occult blood was negative, and there were no further clinical signs of external or internal bleeding.

Over time, the condition of the patient improved, and the creatinine level returned to within the reference range. The patient had sufficient urinary output and did not require dialysis. On day 21 after admission, repeat PCR testing results for SARS-CoV-2 and LASV were negative, and all vital signs were stable. The patient was discharged in good health.

Patient B was a 40-year-old woman who was referred by a peripheral healthcare center to ISTH on March 15, 2021. She came to the hospital because of fever, headache, and loss of appetite. She was empirically given artemether/lumefantrine but symptoms persisted. This finding prompted testing for LASV at ISTH; result was positive (Ct 31.80, by RealStar Lassa Virus RT-PCR Kit).

She had a body temperature of 37.8°C, heart rate (tachycardia) 118 bpm/min, blood pressure 89/69 mm Hg, regular respiration, and 99% oxygen saturation in ambient air. Physical examination showed no additional major pathologic findings.

Antiviral therapy with intravenous ribavirin according to the Irrua regimen was initiated. On day 3 of admission, the patient reported intense headaches and had persistent fever of 38.3°C. Examination showed pronounced neck stiffness that was interpreted as a sign of meningeal irritation. Lumbar puncture was not performed to minimize risk for bleeding in the context of a viral hemorrhagic fever with unknown mechanisms of bleeding and lacking availability for coagulation testing.

Based on a clinical diagnosis of meningitis, the patient was empirically given intravenous ceftriaxone (2 g every 12 h) and intravenous dexamethasone (4 mg every 12 h). Over the next few days, fever and other complaints subsided gradually and vital signs returned to reference ranges. Ceftriaxone and dexamethasone were discontinued after 7 days of treatment. On day 13 of admission, headache and neck stiffness were markedly reduced, and ribavirin was switched to oral therapy. PCR for LASV on day 14 of admission was negative. Ribavirin was then discontinued, and the patient was discharged.

Both patients were seen for follow-up. They appeared to be in good health and recovered without sequelae.

Improved treatment options for Lassa fever are urgently needed because convincing evidence for use of ribavirin is lacking (5,6). Hyperinflammation is a consistent feature in severe Lassa fever (11,12), as well as in other severe viral infections. Because corticosteroids in general, and dexamethasone as a particularly potent derivative, rapidly reduce hyperinflammation, their use might address this pathophysiologic process. Fear of exacerbation of viral replication and thus worsening the outcome of Lassa fever has so far prevented its routine use for Lassa fever.

In the 2 cases reported, dexamethasone was initiated for treatment of concomitant infections, rather than for indication of Lassa fever. No apparent detrimental effects on the clinical course of disease or virologic or laboratory features were observed. Both patients were severely ill, yet recovered after receiving dexamethasone and ribavirin therapy and showed no sequelae. Patient A had considerable risk factors for poor disease outcome of Lassa fever, such as preexisting chronic concurrent conditions and co-infection with COVID-19. The disease course was complicated by anemia and acute kidney injury. Treatment with dexamethasone might have also contributed to reducing hyperinflammation causing or contributing to these pathologies and similarly to the clinical signs of meningeal inflammation in patient B.

Although these 2 cases of severe Lassa fever cannot be interpreted as proven evidence of the benefit of dexamethasone in Lassa fever therapy, we have not observed any considerable side effects, which provides reassurance for safe assessment in future interventional clinical trials. We suggest that future systematic research into the exact pathophysiology of Lassa fever and a systematic clinical investigation of antiinflammatory and immune-modulatory drugs, such as dexamethasone, for ancillary therapy for Lassa fever are warranted.