ABSTRACT
Objective To study the dynamic trajectories of quantitative immunoglobulin G (IgG) titers of hospitalized coronavirus disease 2019 (COVID-19) patients and reveal the immune process of the organism after infection. Methods The clinical data and quantitative IgG titers at different time points of hospitalized COVID-19 patients in Wuhan Huoshenshan Hospital and Guanggu Branch of Maternity and Child Healthcare Hospital of Hubei Province from Feb. 5 to Apr. 15, 2020 were retrospectively analyzed. Group-based trajectory modeling was used to identify the subgroups from time-series data of patients’ antibody titers, and then the clinical characteristics and outcomes were compared among these trajectory groups. Results Totally, 734 patients who met the criteria were included. Three IgG trajectory groups were identified from the antibody data: group 1 (consistently low group, 60 cases［8.17%］), group 2 (moderate group, 38 cases ［5.18%］) and group 3 (high group, 636 cases［86.65%］). The hospitalization days and the virus clearance time of patients in the 3 groups were significantly different (both P＜0.001), those in group 1 were the shortest, while the all-cause mortality and disease deterioration rate had no significant difference in the 3 groups (both P＞0.05). Conclusion Patients with different IgG antibody developmental trajectories may have heterogeneous prognosis and immune process. Patients with consistently higher longitudinal antibody titers may require more medical attention.
ABSTRACT
Background: Multi-gene cancer panels, available since 2013, have been used in routine clinical practice for the past six years. A significant concern in the uptake of panel testing by both clinicians and patients is the possibility of receiving a variant of uncertain significance (VUS). There are no published standard VUS rates, however, labs have anecdotally reported a rate of 1–1.3% per gene. The VUS rate in cancer panels has fallen drastically since the introduction of testing. This rate may continue to fall with the implementation of data sharing platforms, like ClinVar. With the exception of founder mutations, pathogenic variant rates are similar across different ethnic groups, however, VUS rates are significantly higher in non-white ethnic groups. In 2017, our center assessed the VUS rate for our mostly urban, ethnically diverse patient population. At that time, out of 478 patients who underwent multi-gene cancer testing, 162 (33.8%) were found to have at least one VUS;the overall VUS to gene ratio was 1.64%. With this study, we aim to observe our current VUS rate in order to assess whether there is a decrease in VUS in our center similar to that observed nationally. Methods: As part of our routine clinical practice, the results of all patients referred for cancer genetic counseling for a personal or family history of cancer are maintained in a secure, HIPPA-compliant database. The entries of all patients who completed a genetics consultation in 2020 were reviewed. Patients were excluded from analysis if they did not pursue genetic testing or if they pursued single gene or single site testing. Patients who completed any multi-gene cancer panel testing were included. The number of genes included in the panels varied due to reported history and patient preference. Results were analyzed for presence or absence of pathogenic variants and VUS. Results: In 2020, 768 patients completed a cancer genetics consultation. The majority of our patients (624/768 or 81%) reside in the Bronx. 20 patients (3%) reside in other New York City (NYC) boroughs and the remaining 124 patients reside outside of NYC. Of the 768 patients, 450 (59%) had a personal history of cancer and 318 (41%) had a family history of cancer only. A total of 307 were excluded from analysis: 160 patients declined genetic testing. An additional 147 patients were excluded, (26 with abnormal results from testing performed by outside providers, 10 who pursued single site testing, 8 who canceled testing due to billing concerns, 48 who missed their blood draw appointments, and 17 who did not return their saliva kits). Moreover, 1 patient passed away before completing testing and 36 had results pending. Out of 461 patients who completed cancer panel testing, 51 (11%) were found to have a pathogenic variant and 171 (37%) were found to have at least one VUS;a total of 213 VUS were noted, as some patients were found to have more than one VUS. Of note,13 of these individuals were also found to have a pathogenic variant. A total of 17,613 genes were tested through all the cancer panels ordered, which yields a variant rate of 1.21%. The most common identified VUSs were in the following genes: ATM (18/171, 11%, one patient had 2 ATM VUSs);BRCA2 (12/171, 7%);APC (14/171, 8%, one patient had 2 APC VUSs);DICER1 (11/171 or 6%, one patient had 2 DICER1 VUSs);BARD1 (11/171, 6%);CHEK2, MSH2, and RAD51D (each with 10/171, 6%). Discussion: As compared to 2017, the number of patients receiving a VUS on their multi-gene cancer panel testing increased to 37%, as compared to 34%. The variant to gene ratio decreased, however, to 1.2% as compared to 1.6%. One likely explanation for this apparent contradiction is the fact that larger, more comprehensive cancer gene panels are being offered now as compared to the outset of the testing, as many patients and providers favored smaller, more targeted panels and many labs have increased the number of genes on the panels they offer. Therefore, while the overall variant rate per gene has decreased, more of our patients are faced with receiving a VUS result and coping with the anxiety and other negative psychological impacts. Limitations to these data include the COVID-19 pandemic. In 2020, with the suspension of elective procedures and scheduling limitations, the ability of our center to complete cancer consultations was suspended and/or significantly reduced for many months. Therefore, patients seen for cancer genetic counseling may have been more likely to have a personal history of cancer or a stronger family history of cancer, however, it is unclear if this would affect the noted VUS rate. Conclusions: This study highlights the importance of pre and posttest counseling as well as ongoing vigilance with VUS rates, especially in an ethnically diverse population. It also makes the sharing of data between clinical laboratories more imperative in order to attempt to further reduce these rates.