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Letters to the Editor
Incidence and outcome of SARS-CoV-2 infection in patients with monoclonal gammopathy of undeter- mined significance: a case-control study
In March 2020, "Coronavirus Disease 2019" (COVID- 19) outbreak due to SARS-CoV-2 was declared a pan- demic by the World Health Organization. Clinical mani- festations of COVID-19 are variable, ranging from com- plete absence of symptoms, to severe pneumonia, multi- organ failure, and death. Main risk factors for poor out- come of COVID-19 are advanced age and comorbidities, conditions that often recur in patients with monoclonal gammopathies. In this setting, several papers have reported more frequent and severe COVID-19, as well as higher fatality rate, in patients with multiple myeloma (MM), particularly in those older than 60 years, with high risk, active/progressive disease and/or renal failure, respect to general population.1-3 By contrast, very few data are available about patients with monoclonal gam- mopathies of undetermined significance (MGUS).4 In our retrospective study, we investigated the incidence of SARS-CoV-2 infection and COVID-19 outcomes in MGUS patients. Overall, we found that subjects with MGUS neither have an increased risk of contracting SARS-CoV-2, nor show poorer COVID-19 outcomes compared to controls.
Patients with MGUS are frequently asymptomatic and diagnosed by chance; therefore, differently from MM, one would not expect an increased incidence of SARS- CoV-2 infection or a worse outcome of COVID-19 respect to the normal population in these subjects. Notwithstanding, according to well recognized risk fac- tors, they may have different risks of developing MM, as well as clinical findings, including older age, presence of medical comorbidities, and impaired humoral/cellular immunity, which could still play a role when assessing their risk during the COVID-19 pandemic.5,6 Notably, in epidemiological studies, people with MGUS were shown to have an increased risk of developing both venous and arterial thrombosis, bacterial and viral infec- tions, as well as an excess mortality risk due to bacterial infections as compared to age and sex-matched healthy controls.7,8 On this basis, the presence of MGUS could possibly increase susceptibility to SARS-CoV-2 infection and severity of COVID-19, and might theoretically account for the increased mortality due to COVID-19 observed in the elderly population.9 However, a retro- spective chart review aiming to study the vulnerability of 228 patients with MGUS (3 of whom resulted infected by SARS-CoV2, with 1 death) and their clinical out- comes during the COVID-19 pandemic, concluded that there were neither significant differences in the mean age or survival of the MGUS patients not infected by SARS-COV-2 who died before versus after the pandemic onset, nor an increase in venous thrombotic events.10 Furthermore, in a small case series of seven MGUS patients experiencing COVID-19, 71% were hospital- ized, but none of the patients required mechanical ven- tilation or ICU (intensive care unit) management.4 Patients had an age range between 59 and 92 years and all had underlying high-risk comorbidities. One patient with acute kidney injury recovered after hemodialysis. The only death was a male patient with advanced age, nursing home residency, multiple comorbidities and ele- vated D-dimer. This small case series would suggest that MGUS does not pose additional risks for poor outcome in COVID-19 patients.
The aim of our observational, retrospective, single
center study was to formally investigate the incidence of SARS-CoV-2 infection, as well as the characteristics and the clinical outcome of COVID-19 in a larger cohort of MGUS patients. The study was conducted within the context of the clinicaltrials gov. Identifier: NCT04352556.
Between March 1, 2020 and April 30, 2021, we col- lected, among 1.454 MGUS patients followed at our cen- ter, clinical data from 91 patients with SARS-CoV2 infec- tion, diagnosed by RT-PCR on nasopharyngeal swabs. Data were mainly extracted from “GIAVA-COVID-19”, a regional platform where authorized medical health workers can view the results of the nasopharyngeal swabs for SARS-CoV-2 performed, along with other information. In MGUS patients a review of medical records was also carried out. Clinical data collected regarded age, cardiovascular, pulmonary, diabetic and neoplastic comorbidities, presence of symptoms (in detail: fever or chills, cough, shortness of breath or diffi- culty breathing, fatigue, muscle or body aches, headache, loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, diarrhea), hospital- ization, hospitalization in ICU, and outcome (alive/dead). Patients with monoclonal gammopathies of clinical (renal, dermatological or neurological) signifi- cance (MGCS) were excluded.
The characteristics of COVID-19 in MGUS patients were compared with those of 182 age- and sex-matched normal controls infected by SARS-CoV-2. Furthermore, the incidence of SARS-CoV-2 infection in MGUS patients was compared to that of the entire Apulian pop- ulation (Apulia is a region of Southern Italy with about 4 million inhabitants). Wilcoxon test, chi-square tests and multivariate logistic regression were applied, as appro- priate, by using STATA software MP17.
Table 1 summarizes the main characteristics of SARS- CoV-2 infected MGUS patients and controls. The two groups were comparable for age, sex, and presence of comorbidities. Among the MGUS group, 68 patients showed a non-IgM subtype and nine an IgM subtype: this information was missing in five patients. Nine patients had a double M-component. Immunoparesis (at least one uninvolved immunoglobulin below reference levels) was present in 19% of 68 evaluable patients. Regarding MGUS risk-stratification according to Mayo Clinic model, most (94%) of 47 patients with complete available dataset scored as low or low/intermediate risk. Sixty-two patients showed the presence of at least one co-existing, potentially clinically relevant comorbidity (cardiovascular disease 40.6%, diabetes 11%, non- hematological cancer 8.8%, pulmonary disease 6.6%).
As shown in Table 1, rates of COVID-19-related symptoms, hospitalization, hospitalization in ICU and deaths due to COVID-19 were slightly higher in the MGUS group than in the control group, but these differ- ences were not statistically significant. In MGUS patients, sex, immunoparesis, presence/number of comorbidities and IgM versus non-IgM isotype did not significantly influence the risk of death, while a statisti- cally significant association was observed with older age; importantly, the risk of death was not correlated with the presence of MGUS (Table 2). Lastly, incidence of SARS-CoV2 infection in MGUS patients (91/1.454, 6.2%) was not statistically different from that observed in the entire population of the Apulia region (227.761/3.926.931, 5.8%) during the same period (Table 1).
Thus, in our study, patients with MGUS, contrarily to what is seen in MM, did not show an increased incidence
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