Altered immune response to vaccination in patients with plasma cell premalignancy

Introduction Patients with hematological malignancies, including multiple myeloma (MM), experience suboptimal responses to SARS-CoV-2 vaccination. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM) are precursors to MM and exhibit altered immune cell composition and function. The SARS-CoV-2 pandemic and the subsequent population-wide vaccination represent an opportunity to study the real-life immune response to a common antigen. Here, we present updated results from the IMPACT study, a study we launched in November 2020 to characterize the effect of plasma cell premalignancy on response to SARS-CoV2 vaccination (vx). Methods We performed: (i) ELISA for SARS-CoV-2-specific antibodies on 1,887 peripheral blood (PB) samples (237 healthy donors (HD), and 550 MGUS, 947 SMM, and 153 MM patients) drawn preand post-vx;(ii) single-cell RNA, T cell receptor (TCR), and B cell receptor (BCR) sequencing (10x Genomics) on 224 PB samples (26 HD, and 20 MGUS, 48 SMM, and 24 MM patients) drawn preand post-vx;(iii) plasma cytokine profiling (Olink) on 106 PB samples (32 HD, and 38 MGUS and 36 SMM patients) drawn pre- and post-vx;and (iv) bulk TCR sequencing (Adaptive Biotechnologies) on 8 PB samples from 4 patients (2 MGUS, 2 SMM) drawn pre- and post-vx. Results Patients with MGUS and SMM achieved comparable antibody titers to HD two months post-vx. However, patient titers waned significantly faster, and 4 months post-vx we observed significantly lower titers in both MGUS (Wilcoxon rank-sum, p=0.030) and SMM (p=0.010). These results indicate impaired humoral immune response in patients with MGUS and SMM.At baseline, the TCR repertoire was significantly less diverse in patients with SMM compared to HD (Wilcoxon rank-sum, p=0.039), while no significant difference was observed in the BCR repertoire (p=0.095). Interestingly, a significant increase in TCR repertoire diversity was observed post-vx in patients with SMM (paired t-test, p=0.014), indicating rare T cell clone recruitment in response to vaccination. In both HD and patients, recruited clones showed upregulation of genes associated with CD4+ naive and memory T cells, suggesting preservation of the T cell response in SMM, which was confirmed by bulk TCR-sequencing in 4 patients.Lastly, by cytokine profiling, we observed a defect in IL-1beta and IL-18 induction post-vx in patients with SMM compared to HD (Wilcoxon rank-sum, p=0.047 and p=0.015, respectively), two key monocyte-derived mediators of acute inflammation, suggesting an altered innate immune response as well. Conclusion Taken together, our findings highlight that despite the absence of clinical manifestations, plasma cell premalignancy is associated with defects in both innate and adaptive immune responses. Therefore, patients with plasma cell premalignancy may require adjusted vaccination strategies for optimal immunization.

Initial High Sensitivity Troponin I Values Predict 28 Day Survival in Coronavirus-19 Patients

Objectives: To determine the 28 day survival prognostic value of the initial Emergency Department (ED) high sensitivity cardiac troponin I (hs-cTnI) measurement in coronavirus-19 disease 2019 (COVID-19) patients. Background(s): Recent reports indicate that the presence of cardiac injury [troponin level > the 99th percentile upper reference limit (99th % URL) using mostly contemporary assays] is predictive of death within 30 days during hospitalization of COVID-19 patients. Troponin values ordered in the ED or after hospitalization were used for these analyses. Method(s): Using an ED centric electronic database of COVID-19 patients (nasopharyngeal swab testing within 1 week prior to or during the ED visit) having at least 1 hs-cTnI (Beckman Coulter, Brea, CA;level of quantitation (LoQ) 4ng/L, non sex specific 99th percentile URL 18 ng/L) value reported during a visit to an urban, academic ED in the United States. All patients were followed for 28 days to determine all-cause mortality. Kaplan Meir survival curves were constructed to compare outcomes amongst predetermined initial hs-cTnI value intervals. Result(s): From March 16-November 2, 2020 1476 consecutive ED COVID-19 patients were identified with 1044 (70.7%) having at least 1 hs-cTnI value resulted in the ED. Patients' mean age and body mass index were 60.8 +/- 16.1 years and 32.4 +/- 11.3 kg/m2 respectively. 531 (50.9%) were male, 804 (77.0%) self-identified as African American and 615 (58.9%) had 2 or more comorbidities with hypertension (42.5%), diabetes (37.4%) and hyperlipidemia (27.23%) commonest. Hs-cTnI interval values were: 147 (14.1%) < 4 (LoQ), 359 (34.4%) 4-10 and 151 (14.5%) 11-18 ng/L. Hs-cTnI values were > 99th % URL in 387 (37.1%) patients with 230 (22.0%) 19-54, 63 (6.0%) 54-99 and 94 (9.0%) = 100 (laboratory reported critical value) ng/L. 145 (13.9%) patients were discharged directly home and 2 (0.2%) died in the ED. 147 (14.1%) were admitted to an ICU with 104 (70.7%) dying. Each of the interval initial ED hs-cTnI values was associated with a different (p < 0.001) 28 day survival curve (Figure). Conclusion(s): Most COVID-19 patients had a hs-cTnI value obtained with 85.9% of these > 4 ng/L. No one with an initial hs-cTnI < 4 ng/L died within 28 days while increasing presenting hs-cTnI values > 4 ng/L were associated with decreased 28 day survival. Our findings indicate that in COVID-19 patients detectable initial ED hs-cTnI values, whether reaching thresholds for cardiac injury or not, are highly prognostic of 28 day survival.Copyright © 2023

High sensitivity troponin I and newly/recently diagnosed coronavirus-19 disease patients presenting to the emergency department: Values above and below the 99th percentile predict 28 day mortality

Background: Studies indicate that the presence of cardiac injury [troponin level > the 99th percentile upper reference limit (99th % URL) using mostly contemporary assays] is predictive of death within 30 days during hospitalization of coronavirus disease 2019 (COVID-19) patients. Troponin measurements in these reports were ordered and/or resulted in the Emergency Department (ED) or during various times after hospital admission and not all patients were followed for 30 days. Purpose(s): Our objective was to determine the 28 day survival prognostic value of Emergency Department (ED) resulted high sensitivity cardiac troponin I (hs-cTnI) measurements in all COVID-19 patients including those discharged after their ED visit or hospitalization. Method(s): An ED centric electronic database of COVID-19 patients (nasopharyngeal swab testing within 1 week prior to or during the ED visit) having at least 1 hs-cTnI (Beckman Coulter, Brea, CA;level of quantitation (LoQ) 4ng/L, non sex specific 99th % URL 18 ng/L) value reported during a visit to an urban, academic ED in the United States was constructed. All patients were followed for 28 days and Kaplan Meir survival curves constructed amongst predetermined initial hs-cTnI value intervals. Result(s): From March 16-November 2, 2020 1476 consecutive ED COVID- 19 patients were identified with 1044 (70.7%) having at least 1 hs-cTnI value resulted in the ED. Patients' mean age and body mass index were 60.8+/-16.1 years and 32.4+/-11.3 kg/m2 respectively. 531 (50.9%) were male, 804 (77.0%) self-identified as African American and 615 (58.9%) had 2 or more comorbidities with hypertension (42.5%), diabetes (37.4%) and hyperlipidemia (27.23%) commonest. Frequent primary presenting complaints were shortness of breath (37.7%), fever/chills (14.5%) and cough (11.9%). Hs-cTnI interval values were: 147 (14.1%) <4 (LoQ), 359 (34.4%) 4-10 and 151 (14.5%) 11-18 ng/L. Hs-cTnI values were >99th % URL in 387 (37.1%) patients with 230 (22.0%) 19-54, 63 (6.0%) 54-99 and 94 (9.0%) >=100 (laboratory reported critical value) ng/L. 145 (13.9%) patients were discharged directly home and 2 (0.2%) died in the ED. 147 (14.1%) were admitted to an ICU with 104 (70.7%) dying. Each of the interval initial ED hs-cTnI values was associated with a different (p<0.001) 28 day survival curve. Conclusion(s): Most COVID-19 patients had a hs-cTnI value obtained with 85.9% of these >4 ng/L. No one with an initial hs-cTnI <4 ng/L died within 28 days while increasing presenting hs-cTnI values >4 ng/L were associated with decreased 28 day survival. Our findings indicate that in COVID-19 patients detectable initial ED hs-cTnI values, whether reaching thresholds for cardiac injury or not, are highly prognostic of 28 day survival. Studies are needed to better define how hs-cTnI values could alter early management of COVID-19 disease to improve outcomes for these patients. (Figure Presented).

Effectiveness of Eculizumab Treatment for Generalized Myasthenia Gravis in Us Clinical Practice: GMG Registry Data

INTRODUCTION: Clinical trial data have demonstrated that eculizumab improves clinical outcomes in individuals with refractory generalized myasthenia gravis (gMG). Data from clinical practice on treatment patterns and effectiveness of eculizumab in gMG are being collected by the Alexion-sponsored gMG Registry. OBJECTIVE: To describe treatment outcomes and safety (serious adverse events [SAEs]) in current gMG Registry participants during eculizumab therapy in clinical practice in the USA. METHODS: Starting in December 2019, adults with gMG who had ever received eculizumab enrolled in the gMG Registry (NCT04202341). After obtaining consent, demographic data, myasthenia gravis activities of daily living (MG-ADL) total score and Myasthenia Gravis Foundation of America (MGFA) classification were collected from medical records at two time points: In the 6 months before eculizumab initiation and at first gMG Registry assessment after eculizumab treatment initiation (at Registry enrollment). SAEs in patients receiving eculizumab during Registry participation were recorded. RESULTS: As of November 29, 2021, in total, 111 adults with gMG had enrolled in the gMG Registry (male, 52.3%;mean [range] age at MG diagnosis, 56.1 [16.0-92.0] years). The mean (range) time from eculizumab initiation to gMG Registry enrollment was 2.0 (0.0-6.7) years. Mean (standard deviation) MG-ADL total score decreased from 8.3 (3.6) before eculizumab initiation to 3.1 (3.6) after eculizumab treatment. MGFA classification improved with eculizumab treatment: Class I, 0.0% of patients before eculizumab initiation versus 28.9% after eculizumab treatment;class II, 36.8% versus 55.3%;class III, 52.6% versus 15.8%;class IV, 10.5% versus 0.0%. The median MGFA class was III before eculizumab initiation and II after eculizumab treatment. One SAE (invasive pulmonary aspergillosis) considered by the investigator to be related to eculizumab was reported in a patient who died, and two serious infections considered unrelated to eculizumab were reported (COVID-19/pneumonia and urinary tract infection);there were no meningococcal infections. Two patients died of causes considered to be unrelated to eculizumab (lung adenocarcinoma and acute congestive heart failure/myocardial infarction). CONCLUSION: These data from the gMG Registry provide evidence of the effectiveness of eculizumab for the treatment of gMG in clinical practice across the USA, demonstrating a benefit/risk profile consistent with that observed in clinical trials.

Humoral SARS-CoV-2 response in asymptomatic precursor plasma cell dyscrasia patients: IMPACT study results

Introduction: Patients with hematologic malignancies, including multiple myeloma (MM), experience worse SARS-CoV-2 infection outcomes and sub-optimal vaccine responses. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) precede MM and affect ∼5% of individuals age >=50. We previously showed that individuals with MGUS and SMM exhibit immune dysregulation. Here, we investigate the immune response to SARS-CoV-2 vaccination in these asymptomatic but potentially immunocompromised individuals. Methods: The IMPACT study (IRB #20-332) is a prospective study at Dana-Farber Cancer Institute in collaboration with MMRF, which enrolled individuals nationwide with a diagnosed plasma cell dyscrasia and healthy individuals. As of October 2021, 3,005 individuals completed a questionnaire regarding prior infection or vaccination. We obtained 1,350 blood samples from 628 participants and analyzed anti-SARS-CoV-2 IgG antibody titer by ELISA. Results: 2,771 (92%) participants were fully vaccinated (2 doses BNT162b2 or mRNA-1273;1 dose Ad26.COV2.s), 269 (9%) had received a 3rd mRNA vaccine dose, and 234 (8%) were unvaccinated. 1,387 (46%) and 1,093 (36%) participants received mRNA vaccines (BNT162b2 and mRNA-1273), and 139 (5%) participants received an adenovirus vector vaccine (Ad26.COV2.S). 34 (1%) individuals reported SARS-CoV-2 infection after full vaccination. We measured antibody titers in 201 MGUS, 223 SMM, 40 smoldering Waldenstrom macroglobulinemia (SWM), 64 MM, and 100 healthy controls. Multiple linear regression model estimated the association between various clinical variables and post-vaccination antibody titers. As previously reported, having MM was associated with low antibody titer (p < 0.001). Of note, having SMM, regardless of risk stratification by 2/20/20 criteria, was also associated with low antibody titers, indicating that even low-risk SMM patients have a poor response to vaccination. MGUS and SWM diagnoses were not significantly associated with antibody titers. Additionally, male sex (p < 0.010), elapsed time after vaccination (p < 0.001), and BNT162b2 vaccine (p < 0.001) were associated with low antibody titers. SARS-CoV-2 infection prior to vaccination was associated with high antibody titers. We identified 25 patients (6 MGUS, 10 SMM, 2 SWM, 7 MM) who submitted blood samples after both the 2nd and 3rd dose. In these patients we observed a significant increase in antibody titer after a 3rd dose (p = 0.002). We also observed that antibody titers of patients after a 3rd dose (13 MGUS, 12 SMM, 2 SWM, 31 MM) were comparable to that of healthy individuals after a 2nd dose (p = 0.833). Conclusion: Our data indicates that suboptimal response to SARS-CoV-2 does not only occur with MM and cancer patients receiving therapy but also in precursor asymptomatic patients including low-risk SMM.

Real-world experience of eculizumab treatment for generalized myasthenia gravis: initial data from a registry of patients with generalized myasthenia gravis in the USA

Objective: To describe the baseline characteristics and interim treatment outcomes of registry participants with generalized myasthenia gravis (gMG) treated with eculizumab in real-world clinical practice in the USA. Background: Clinical trials have shown that eculizumab improves clinical outcomes in individuals with refractory gMG. The Alexion-sponsored gMG Registry collects real-world data on treatment patterns and effectiveness of eculizumab in gMG. Design/Methods: Adults with gMG who had ever received eculizumab enrolled in the Alexion-sponsored gMG Registry (NCT04202341) from December 2019. After consent, demographic data, Myasthenia Gravis (MG) activities of daily living (ADL) total scores, MG Foundation of America (MGFA) classification and serious adverse events (SAEs) were collected from medical records at two time points: before eculizumab initiation (within prior 6 months) and at Registry enrollment (first Registry assessment during eculizumab treatment). Results: As of February 28, 2021, 59 adults with gMG had enrolled in the Registry (male, 54.2%;mean [range] age at MG diagnosis, 58.3 [16.0-84.0] years). Mean (range) time from eculizumab initiation to Registry enrollment was 697.1 (7.0-2435.0) days. Mean (standard deviation) MG-ADL total score decreased with eculizumab, from 8.3 (3.71) before eculizumab to 3.1 (3.43) at first Registry assessment during treatment (n=38). MGFA classification improved with eculizumab (n=32): before eculizumab, MG was class I (0.0% of patients), II (40.6%), III (53.1%) or IV (6.3%);at first Registry assessment during treatment, MG was class I (25.0%), II (62.5%), III (12.5%) or IV (0.0%). SAEs (lung adenocarcinoma, respiratory failure, atrial fibrillation, heart failure, colostomy closure, COVID-19, death) were reported in six patients. There were two deaths (unrelated to eculizumab). No meningococcal infections were reported. Conclusions: Initial analyses of Registry data showed that MG-ADL total score and MGFA classification improved with eculizumab, and that eculizumab was generally well tolerated. These findings provide additional evidence of the effectiveness of eculizumab for treating gMG in real-world clinical practice.

A prospective natural history study and biorepository for patients with myasthenia gravis (EXPLORE-MG2)

Objective: To define clinical features, disease course, and collect biospecimens in patients with myasthenia gravis (MG), including understudied subgroups such as seronegative, muscle-specific kinase antibody (MuSK), and LRP4 antibody positive MG. Background: The MG Rare Disease Clinical Research Network (MGNet) was funded by the National Institutes of Health (NIH) to gain better understanding of the clinical course of MG and develop improved approaches to diagnosis and treatment. As part of this initiative a multicenter prospective natural history study and biorepository was developed: Exploring Outcomes and Characteristics of Myasthenia Gravis 2 (EXPLORE-MG2). Design/Methods: EXPLORE-MG2 is a web-based observational registry that incorporates NIH recommended common data elements for MG. Key eligibility criteria include: ≥18 years old;diagnosed with MG within 2-years of study enrollment based on clinical presentation and seropositivity for MG associated autoantibodies, and/or abnormal neurophysiology test or positive edrophonium test. Biospecimen collection focuses on immunosuppressive naïve patients and rare MG subgroups. Participants will be followed for at least 2-years with study visits occurring approximately every 6 months in the context of usual clinical care. The study has been open to enrollment since January 2021 with 6 sites currently activated/participating. Results: A total of 62 patients have been enrolled and 152 biospecimens were collected as of 10/1/2021. The mean age was 57 years (range 20-84);47% were female, 66% were acetylcholine receptor antibody-positive, 16% were MuSK MG, and 18% were seronegative. Enrollment of new participants and follow-up of existing participants are ongoing to reach our current goal of 400 enrolled participants. We will present updated enrollment data and demographics at the meeting. Conclusions: The EXPLORE-MG2 study is active after a COVID-19 pandemic related delay. Samples and clinical data will be available to researchers for current and future investigation. Data from EXPLORE-MG2 will improve clinical trial readiness for future studies and facilitate development of treatment-responsive biomarkers.

All Initial High Sensitivity Cardiac Troponin I Values Are Prognostic for 28 Day Survival in Coronavirus-19 Disease Patients

Study Objectives: Recent reports indicate that the presence of cardiac injury [troponin level > the 99th percentile upper reference limit (99th % URL) using mostly contemporary assays] is predictive of death within 30 days during hospitalization of coronavirus disease 2019 (COVID-19) patients. Troponin values ordered in the emergency department (ED) or after hospitalization were used for these analyses. Our objective was to determine the 28 day survival prognostic value of ED resulted high sensitivity cardiac troponin I (hs-cTnI) measurements in COVID-19 patients. Methods: We established an ED centric electronic database of COVID-19 patients (nasopharyngeal swab testing within 1 week prior to or during the ED visit) having at least 1 hs-cTnI (Beckman Coulter, Brea, CA;level of quantitation (LoQ) 4ng/L, non sex specific 99th percentile URL 18 ng/L) value reported during a visit to an urban, academic ED in the United States. All patients, whether admitted and expired in the hospital or hospital discharged or sent home directly from the ED were followed for 28 days to determine all-cause mortality. Kaplan Meir survival curves were constructed to compare outcomes amongst predetermined initial hs- cTnI value intervals. Results: From March 16-November 2, 2020 1476 consecutive ED COVID-19 patients were identified with 1044 (70.7%) having at least 1 hs-cTnI value resulted in the ED. Patients’ mean age and body mass index were 60.8 ± 16.1 years and 32.4 ± 11.3 kg/m2 respectively. 531 (50.9%) were male, 804 (77.0%) self-identified as African American and 615 (58.9%) had 2 or more comorbidities with hypertension (42.5%), diabetes (37.4%) and hyperlipidemia (27.23%) commonest. Frequent primary presenting complaints were shortness of breath (37.7%), fever/chills (14.5%) and cough (11.9%). Hs-cTnI interval values were: 147 (14.1%) < 4 (LoQ), 359 (34.4%) 4-10 and 151 (14.5%) 11-18 ng/L. Hs-cTnI values were > 99th % URL in 387 (37.1%) patients with 230 (22.0%) 19-54, 63 (6.0%) 54-99 and 94 (9.0%) ≥ 100 (laboratory reported critical value) ng/L. 145 (13.9%) patients were discharged directly home and 2 (0.2%) died in the ED. 147 (14.1%) were admitted to an ICU with 104 (70.7%) dying. Each of the interval initial ED hs-cTnI values was associated with a different (p < 0.001) 28 day survival curve (Figure). Conclusions: Most COVID-19 patients had a hs-cTnI value obtained with 85.9% of these > 4 ng/L. No one with an initial hs-cTnI < 4 ng/L died within 28 days while increasing presenting hs-cTnI values > 4 ng/L were associated with decreased 28 day survival. Our findings indicate that in COVID-19 patients detectable initial ED hs-cTnI values, whether reaching thresholds for cardiac injury or not, are highly prognostic of 28 day survival. Studies are needed to better define how hs-cTnI values could alter early management of COVID-19 disease to improve outcomes for these patients. [Formula presented]

Low prevalence of arrhythmias among healthcare workers who recovered from COVID-19

INTRODUCTION The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause multiple cardiologic complications such as myocardial injury, cardiogenic shock and arrhythmias. In patients admitted to an intensive care unit (ICU), sinus tachycardia and atrial fibrillation are the most commonly reported arrhythmias. However, data on the prevalence of arrhythmias after symptomatic SARS-CoV-2 infection is limited. Using 48-hour electrocardiographic (ECG) Holter monitoring, we aimed to analyse the incidence and types of arrhythmias among healthcare workers who recovered from SARS-COV-2 infection. MATERIAL AND METHODS The study involved 34 healthcare workers from the university hospital, who had SARS-CoV-2 infection confirmed by pharyngeal swab up to 4 months before study onset and who did not need an ICU stay due to the illness. Each subject underwent a 48-hour ECG monitoring and completed a questionnaire on the course of the disease. Cardiac magnetic resonance imaging (CMR) was performed and the presence of potential arrhythmias substrate was assessed. RESULTS We recruited 24 women and 10 men (47% were doctors) in the mean age of 37 ± 11 years old who underwent symptomatic SARS-CoV-2 infection, but did not require hospitalization during illness. The mean time from the positive swab test to the start of 48-hour ECG monitoring was 2.9 ± 0.9 months. The most frequently reported (in 100%), though sparse, were supraventricular premature contractions (SVPCs) (mean 46 ± 64 per person/day). Atrial fibrillation or atrial flutter were not recorded, however supraventricular tachycardia (SVT) was found in 18% of subjects, and the range of the highest frequency of SVTs was 124-179 bpm. There were no ventricular tachycardia episodes. Ventricular premature contractions (VPCs) were found in 28% of participants but were usually sparse (mean number per person 98 ± 252/day). Six participants had more than 100 VPCs/day, and in 1 it exceeded 1000/day. No one had QTc interval longer than 438 ms. 48-hour ECG monitoring revealed a tendency towards sinus tachycardia during activity time, however, the daily rhythm modulation was diminished in only 15% of participants. Significantly higher maximal daily heart rate (P <0.05) was observed in 29% of subjects in whom CMR revealed the presence of late gadolinium enhancement (LGE). The presence of LGE or extended T1 and T2 relaxation times from CMR were not predictors of the increased number of VPCs or SVPCs (P >0.05). No significant atrioventricular conduction disturbances were recorded. CONCLUSIONS The prevalence of arrhythmias in the mid-term observation of not-hospitalized COVID-19 survivors is low. During prolonged 48-hour ECG monitoring of healthcare workers, neither life-threatening nor clinically significant arrhythmias were recorded. Therefore, the arrhythmic burden after infection with SARS-CoV-2 should be considered as marginal.

Early cross-coronavirus reactive signatures of humoral immunity against COVID-19

The introduction of vaccines has inspired hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against SARS-CoV-2, thus we profiled the earliest humoral signatures in a large cohort of acutely ill (survivors and nonsurvivors) and mild or asymptomatic individuals with COVID-19. Although a SARS-CoV-2-specific immune response evolved rapidly in survivors of COVID-19, nonsurvivors exhibited blunted and delayed humoral immune evolution, particularly with respect to S2-specific antibodies. Given the conservation of S2 across 0-coronaviruses, we found that the early development of SARS-CoV-2-specific immunity occurred in tandem with preexisting common I3-coronavirus OC43 humoral immunity in survivors, which was also selectively expanded in individuals that develop a paucisymptomatic infection. These data point to the importance of cross-coronavirus immunity as a correlate of protection against COVID-19.

Unusual echocardiographic evidence of hypercoagulation in usual left atrial appendage as the first and only sign of COVID-19.

Coronavirus disease 2019 (COVID-19) is a condition caused by a novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease's course ranges from entirely asymptomatic to severely ill patients. Hypercoagulation is often a complication of this disease, worsening the prognosis, which is extremely important in patients at higher risk of thromboembolic events, such as atrial fibrillation (AF), where thrombus formation in the left atrial appendage (LAA) is frequent. LAA could be of various sizes, volumes, and shapes, distinguish several morphologies, from which the WindSock LAA is the most frequent. In contrast, thromboembolic complications occur most frequently in patients with AF and the Cactus LAA. We present a clinical case of a 70-year-old woman with an initial negative real-time polymerase chain reaction (RT-PCR) test for SARS-CoV-2, suspicion of device-related infection after dual pacemaker implantation, AF, and LAA without thrombus in the initial transoesophageal echocardiography (TEE). Despite apixaban treatment, spontaneous restoration of sinus rhythm, and WindSock LAA morphology, the sludge in LAA was diagnosed in control TEE. The patient did not present any typical clinical COVID-19 symptoms but re-checked the RT-PCR test for SARS-CoV-2 infection was positive. The described case presents echocardiographic evidence of hypercoagulation as the first and only feature of SARS-CoV-2 condition besides the usual morphological presentation of the WindSock LAA.