Pathology

Monoclonal gammopathy of undetermined significance

Disease

Coronavirus disease 2019 (COVID-19)

Infectious disease (medical specialty)

Monoclonal antibody

Biology

Outbreak

Series (stratigraphy)

Paleontology

Antibody

Virology

Monoclonal

Immunology

Monoclonal gammopathy

2019-20 coronavirus outbreak

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Medicine

British Journal of Haematology

Monoclonal Gammopathy of Undetermined Significance (MGUS) is a pre-malignant clonal plasma cell disorder, with 25–30% life-long risk of progression to multiple myeloma (MM).1 It is usually asymptomatic, but infrequently associated with several serious conditions, such as neuropathies, glomerulonephritis and acquired angioedema.2 Moreover, a higher risk of infection and deep venous thrombosis has been reported in patients with MGUS.3, 4 In recent studies of SARS-CoV-2 infection (COVID-19) in cancer, a higher fatality rate was found,5 especially in haematologic malignancies.6 While not an overt haematologic malignancy, MGUS falls within the spectrum of plasma cell dyscrasias, and has the potential to disrupt immunity and coagulation.3, 4 Therefore, MGUS could affect the course and outcome of COVID-19; however, such association remains unknown. We describe seven patients diagnosed with MGUS who tested positive for COVID-19 from 18 March through 8 April, 2020, at Montefiore Health System, that was the epicentre of the COVID-19 pandemic in the Bronx, New York (Table I). All cases were positive by real-time reverse-transcriptase polymerase chain reaction of nasopharyngeal swabs. DM HTN HTN CLD DM HTN CKD DM HTN CLD CKD CHF DM HTN CKD DM HTN CKD Dementia Case 1: A 59-year-old Hispanic man with low- to intermediate-risk IgG-kappa MGUS, diabetes mellitus (DM) and hypertension (HTN), presented to the Emergency Department (ED) with three days of dry cough, subjective fever and myalgias. He was normotensive, afebrile, with a room-air oxygen saturation (SpO2) of 98%. He did not require hospital admission, was followed-up one month later and his symptoms had resolved. Case 2: A 66-year-old Caucasian woman with low-risk IgG-lambda MGUS, HTN and bronchiectasis presented to the ED with one week of productive cough, subjective fever, wheezing and diarrhoea. She was normotensive, febrile to 38.9°C, with a room-air SpO2 of 98%. Her chest X-ray (CXR) showed chronic changes. She was hospitalized, started on broad-spectrum antibiotics for presumed superimposed pneumonia, and a course of hydroxychloroquine and lopinavir/ritonavir per institutional protocol. Her hospitalization was complicated by non-infectious diarrhoea, which eventually improved, and was discharged to a rehabilitation facility after a 16-day hospitalization. Case 3: An 83-year-old African American (AA) man with high- to intermediate-risk IgA-kappa MGUS, HTN, DM and chronic kidney disease (CKD), presented with altered mental status (AMS) and lethargy noticed a few hours prior to presentation, and six days of dry cough and malaise. He was normotensive, afebrile, with a room-air SpO2 of 80%, which corrected to 96% on a nasal cannula (NC) (4 l/min). His CXR revealed multifocal bilateral infiltrates. Serum glucose was 884 mg/dl. He was started on intravenous fluids and insulin for his hyperosmolar hyperglycaemic state. D-dimers peaked at 20 μg/ml. He received broad-spectrum antibiotics for potential bacterial superinfection. His confusion gradually resolved, oxygen requirements improved and he was discharged home on hospital day eight. Case 4: A 71-year-old man with low- to intermediate-risk IgM-lambda MGUS and HTN presented to his general practitioner's office with dry cough. He was instructed to self-isolate at home, was followed-up one month later and noted his symptoms had resolved. Case 5: An 81-year-old AA woman with low-risk IgG-lambda MGUS, HTN, DM, CKD, congestive heart failure, and pulmonary sarcoidosis presented to the ED with 10 days of dry cough and dyspnoea. She was hypotensive (90/53), afebrile, with a room-air SpO2 of 89% which improved to 99% on a non-rebreather mask (NRB). CXR showed left lung base atelectasis. Acute kidney injury (AKI) was noted. She was hospitalized, started on intravenous fluids with resolution of hypotension, and treated with hydroxychloroquine per institutional protocol. She was transitioned to NC on hospital day 2. Her renal function and oxygenation gradually improved, and she was discharged to a rehabilitation facility after an 11-day hospitalization. Case 6: A 76-year-old Hispanic man with low- to intermediate-risk IgA-lambda MGUS, HTN, DM and CKD presented to the ED with five days of dry cough and dyspnoea. He was hypertensive (181/78 mm Hg), febrile (38.3°C), with a room-air SpO2 of 96%. His CXR showed bibasilar infiltrates. AKI with hyperkalaemia was noted. He was hospitalized and later developed non-ST-elevation myocardial infarction, managed conservatively. His renal function deteriorated and on hospital day 6 haemodialysis was initiated. His renal function gradually improved and he was discharged home on hospital day 25. Case 7: A 92-year-old AA man, nursing-home-resident with low- to intermediate-risk IgG-kappa MGUS, HTN, DM, CKD, epilepsy and dementia presented to the ED with AMS and lethargy noticed a few hours prior to presentation. He had a dry cough, dyspnoea and malaise for one week. He was hypertensive (158/88 mm Hg), afebrile, with a room-air SpO2 of 96%. On examination he was using accessory respiratory muscles. The patient had do-not-resuscitate and do-not-intubate orders and was therefore placed on a NRB. his CXR showed left mid-lower lobe infiltrates. He was admitted, started on broad-spectrum antibiotics and additionally treated for decompensated heart failure. D-dimers peaked at 20 μg/ml. Finally, his family opted for comfort care and he expired on hospital day 13. COVID-19 is a heterogeneous disease that ranges from asymptomatic in some patients to fatal in others. Advanced age, male sex and comorbidities, such as HTN and DM have been identified as risk factors for adverse prognosis. Significant coagulopathy has been observed in severe cases, and elevated D-dimer levels have been shown to have prognostic significance.7-11 In a study performed at our institution, patients with haematologic malignancies and COVID-19 had a higher mortality rate than non-cancer patients.6 We wanted to investigate the effects that MGUS might have on patients with COVID-19. Our patients were older adults with an age range between 59 and 92 years. They all had underlying conditions, identified as high-risk comorbidities, yet none of the patients required mechanical ventilation or ICU management, and with the exception of one fatality, they all eventually recovered (Table I). The only fatality was a patient with multiple risk factors, including male sex, advanced age, nursing home residency, multiple comorbidities and a very elevated D-dimer. MGUS represents the earliest stage of plasma cell dyscrasia and is generally an asymptomatic phase of the disease spectrum. Still, some studies suggest MGUS patients manifest increased susceptibility to bacterial and viral infections, as well as coagulation abnormalities.3, 4 Whether these perturbations of immunity and coagulation have the potential to impact the clinical trajectory of COVID-19 remains to be examined with large-scale data. This small case series seems to suggest that MGUS may not pose additional risks for poor outcome in COVID-19 infection. The authors declare no competing financial interests. AV, NK and IM conceived the research; AV, VM, RK, LBR, MG, AS, RAS, KG, IB and SJ identified the cases and provided clinical information; JGL collected the data; JGL, NK, IM and AV wrote the manuscript. All the authors reviewed and approved the final version of the manuscript.

A case series of Monoclonal Gammopathy of Undetermined Significance and COVID‐19