A 42-year-old Caucasian male with no medical history was referred to the internal medicine department because of renal failure, a normocytic anemia and persistent malaise after a recent SARS-CoV-2 infection.
Four weeks prior to presentation our patient had experienced a mild episode of COVID-19, as confirmed by reverse-transcription polymerase chain reaction testing (RT-PCR). However, there were persistent complaints of weakness, dyspnea on exertion, anorexia and shivering. History also revealed that shortly after the COVID-19 symptoms started, painless purple spots had appeared on his lower extremities and later on dissolved spontaneously. The patient had no history of alcohol consumption and cigarette smoking. Laboratory test results showed anemia (hemoglobin: 10.3 g/dL), thrombocytopenia (90,000/mm3), impaired kidney function (creatinine: 2.19 mg/dL), mildly elevated C-reactive protein (33 mg/L) and a highly elevated erythrocyte sedimentation rate (116 mm/hour). Urinalysis only revealed moderately increased albuminuria with an albumin-to-creatinine ratio of 188 mg/g. Kidney ultrasound showed no abnormalities.
Additional blood tests aimed at autoimmune disease, multiple myeloma and thrombotic microangiopathies were performed and revealed a type I cryoglobulinemia which was clearly positive, also on repeated testing (Fig. 1). The cryoprecipitate was composed of biclonal IgM (kappa and lambda) without complement components or rheumatoid factor activity. All other tests came back negative, including ANA, anti-dsDNA, ANCA, complement proteins C3 and C4 and serology for hepatitis B, hepatitis C and HIV.
In search of an underlying lymphoproliferative disorder, that nearly all patients with Type I IgM cryoglobulinemia have, we performed a computed tomography (CT) scan and a bone marrow evaluation including cytomorphology, immunophenotyping and biopsy. However, these investigations failed to demonstrate evidence for clinical lymphoma or a culprit clonal population.
Because of the absence of a lymphoproliferative disorder and the suspicious time relation between COVID-19 infection and the cryoglobulinemia, we tested the cryoprecipate for the presence of SARS-CoV-2 antibodies. After extensive washing the cryoprecipitate was resolved, and analysis showed that the immunoglobulins in the cryoprecipitate were in fact directed against SARS-CoV-2 Spike protein (Fig. 2).
In the meanwhile, our patient had noticed improvement of his symptoms accompanied by resolution of his laboratory abnormalities, and the planned renal biopsy was canceled. Four weeks after the initial presentation his kidney function had completely normalized, and the acute phase reactants had dropped considerably. Lastly, the anemia started to resolve. During follow-up 3 months later, our patient was still doing well and the cryoglobulin could no longer be detected.