Genetic risk factors associated with SARS-CoV-2 susceptibility in multiethnic populations

Susceptibility to infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes the disease COVID-19, may be understood more clearly by looking at genetic variants and their associations to susceptibility phenotype. I conducted a genome-wide association study of SARS-CoV-2 susceptibility in a multiethnic set of three populations (European, African, and South Asian) from a UK BioBank clinical and genomic dataset. I estimated associations between susceptibility phenotype and genotyped or imputed SNPs, adjusting for age at enrollment, sex, and the ten top principal components of ancestry. Three genome-wide significant loci and their top associated SNPs were discovered in the European ancestry population: SLC6A20 in the chr3p21.31 locus (rs73062389-A;P=2.315 x 10-12), ABO on chromosome 9 (rs9411378-A;P=2.436 x 10-11) and LZTFL1 on chromosome 3 (rs73062394;P=4.4 x 10-11);these SNPs were not found to be significant in the African and South Asian populations. A multiethnic GWAS may help elucidate further insights into SARS-CoV-2 susceptibility.

Pulmonary thromboendarterectomy after COVID-19 infection: USA single center experience

Background: The safety and efficacy of pulmonary thromboendarterectomy (PTE) surgery after COVID-19 infection is unknown. Objective(s): Assess the outcomes of PTE in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who had COVID-19 infection. Method(s): Retrospective, chart review of PTE cases at UCSD from March 2020 through December 2021. Result(s): 315 patients underwent PTE surgery during the analysis period;23 cases (7.3%) had previous COVID-19 infection. All were asymptomatic from COVID-19 infection at time of surgery. Mean age was 46 (range 16-75;mean 55 for non-COVID group), 13 women, 10 men, mean BMI 34.8 +/- 8.1 (mean 30.7 +/- 7.5 non-COVID). 12 patients (52.2%) were on PH targeted therapy (50.5% non-COVID). Preoperative PVR was 479.2 +/- 288.4 dynes s cm (536.6 +/- 353.7 dynes s cm non-COVID);postoperative PVR was 192.7 +/- 77.1 dynes s cm (216.6 +/- 105.6 dynes s cm non-COVID). Average circulatory arrest time was 40.3 +/- 17.9 minutes (45.3 +/- 19.7 minutes non-COVID, p=0.2), with majority of cases having Level 2 UCSD surgical classification. Average ventilator time was 1.9 days (2.2 days non-COVID, p=0.7), ICU stay 4.4 days (4.4 days non-COVID, p=1.0), length of hospitalization 10.9 days (11.6 days non-COVID, p=0.4). There was 1 case (4.3%) of airway hemorrhage, 3 cases (13.0%) of reperfusion lung injury, and 2 cases (8.7%) of post-operative respiratory infection. 10 patients (43.5%) were discharged on supplemental oxygen (60.0% for non-COVID). There were no in-hospital deaths. Compared with cases operated without COVID-19 infection over the same time period, no major differences were observed. Conclusion(s): History of COVID-19 infection did not affect outcomes of PTE surgery.

Significant decline in cancer diagnostic testing in U.S. CMS population during the COVID-19 pandemic

Background: The COVID-19 pandemic has caused >400,000 infection related deaths in the US to January 2021. Actions taken to limit COVID-19 infection and mortality could potentially lead to unintended consequences, precipitating excess mortality due to other causes. One such cause is delayed cancer diagnosis. Significant decreases in presentation for cancer diagnosis at the primary care level have been noted in the UK. This study aimed to look for evidence of a similar effect in the US. Methods: CMS claims data from JAN18-JUN20 associated with primary diagnosis across 11 cancers (bladder, breast, cervical, colorectal, endometrial, lung, ovarian, pancreatic, prostate, sarcoma and thyroid) were analyzed for use of surgical pathology (SP), a procedure associated with initial diagnosis, and immunohistochemistry (IHC). Test volumes varied widely by test and cancer so were normalized to enable comparison across indications. This was done by dividing the month-on-month difference for the period JAN19-JUN19 vs JAN20-JUN20 by the median monthly test volume for the period JAN18-DEC19 (“pre-COVID period”). Extent and duration of declines in test rates and number of missing patients as the sum of these declines were then determined. The ratio of IHC to SP testing was taken to determine any decline in likely post-initial diagnosis testing. Results: There were significant (>10%) declines in test volumes for SP for all 11 cancers at some time in Q1- Q2 2020. Table. Extent, duration and return to preCOVID levels for SP testing across 11 cancers Median extent and duration of the decline was 56% (range 41.1%-80.4%) and 2 months (range 1- >4). This equates to 32,192 missing diagnoses across all cancers. SP test volumes for all cancers except lung and breast had returned to around pre-COVID levels by JUN20. There was no significant (>10%) increase in normalized SP test volume after the COVID dip for any cancer. While SP showed decreased test volumes across all cancers at some point during the first half of 2020, test volume ratios of IHC to SP showed increases for most cancers in the same time period. Conclusions: These data highlight that the decline in patients presenting to their primary care physicians with suspicion of cancer for diagnostic investigation was linked to COVID-19 prevention strategies. No evidence for increased, “catch up” testing to address presentational/diagnostic backlog was observed. Thus, it is predicted that these patients may subsequently present with a more advanced cancer. Potential excess morbidity, mortality and cost associated with absent or delayed diagnosis should be factored into cancer control programs going forward. (Table Presented).

Clinical impact of tocilizumab therapy in SARS-CoV-2 respiratory infections in ICU and non-ICU patients

Background: Tocilizumab (TCZ) is a monoclonal antibody against the interleuikin- 6 receptor which is potentially beneficial in COVID-19 induced cytokine release syndrome (CRS). However, there are limited studies showing anti-inflammatory effect and clinical benefit of TCZ in COVID-19 patients. This retrospective study examines treatment responses of criteria based TCZ therapy for SARS-CoV-2 respiratory infection for ICU vs. non-ICU patients. Methods: We established institutional criteria to identify patients at risk of CRS from COVID-19. Patients were included if they received at least 1 dose of TCZ and were admitted for at least 72 hours. Primary endpoint was to assess clinical improvement (CI) at the end of admission. CI was defined by extubation, downgrade from ICU, discharged or improvement in Clinical Ordinal Scale by 2. Secondary endpoint of the study was to assess inpatient mortality (IM) and risk factors associated with IM. Subgroup analysis included impact of early (< 96 hours) vs late (≥ 96 hours) TCZ therapy on IM. Results: Between March 25 to May 6, 2020, 170 patients met criteria and received TCZ. There were 83 non-ICU patients and 87 in the ICU. Forty five patients needed invasive mechanical ventilation (IMV). ICU patients tended to be obese, receive 2 doses of TCZ and have longer length of stay. Overall CI was seen in 71% of patients. CI was higher in non-ICU vs ICU patients (85.5% vs 57.5%, P=0.002). Overall IM was 18.8%;however, IM was lower in non-ICU vs ICU patients (8.4% vs 28.7%, P=0.0014). IM was higher in patients on IMV vs. non-IMV (30% vs 15.4%, P=0.03). Risk factors of ICU admission, BMI ≥ 30 kg/m2 and AKI were associated with higher risk of IM. Many IM patients were made comfort care. No differences were observed in early vs late TCZ therapy on inpatient mortality, but there was a trend toward lower mortality with early TCZ. COS Review of Tocilizumab Patients Conclusion: TCZ is an effective treatment option in patients with SARS-CoV-2 patients at risk of CRS. Patients receiving TCZ in non-ICU setting had a better response to treatment compared to ICU patients. Obesity and AKI were associated with higher risk of mortality, but there was no statistical difference in early vs late therapy. Further studies with control group and larger sample size are warranted.

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future.

BACKGROUND: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. MATERIALS AND METHODS: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. RESULTS: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. CONCLUSIONS: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe.