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January 11 | Daily COVID-19 LST Report

Epidemiology

· Do we need routine COVID-19 testing of Emergency Department staff? A study from the University of Washington uses a mathematical model based on the Diamond Princess cruise ship data to predict detection of SARS-CoV-2 in asymptomatic health care workers (HCWs) in the emergency department in regions with high COVID-19 rates. Results revealed that within six months, weekly testing in asymptomatic HCWs would reduce infection rates by 3 to 5.9% when the transmission constant is 1.219e-4 new infections/person^2, while a transmission constant of 3.660e-4 new infections/person^2 would result in reduction of infections by 11 to 23%. The authors urge more frequent testing in asymptomatic HCWs to help reduce the rate of SARS-CoV-2 infection.

Understanding the Pathology

· Dynamic changes are witnessed in anti-SARS-CoV-2 antibodies during SARS-CoV-2 infection and recovery in a retrospective analysis by bioinformatics and global health specialists in Jiangsu, China where 1,850 hospitalized patients with COVID-19 were analyzed and those with mild or moderate disease were found to develop IgG antibodies one week earlier than patients with severe disease. While spike protein and receptor-binding domain specific IgG levels were 1.5- and 2-fold higher in critically ill hospitalized patients and SARS-CoV-2 RNA-negative recovered patients, respectively, compared to those who are remained RNA-positive. These data suggest earlier development of antibodies may be protective against developing severe disease; however, those who recover from more severe disease may also have higher levels of antibodies and a shorter duration of viral shedding.

Management

· Coronary calcium scoring was found to be a predictor for outcome in COVID-19. A retrospective cohort study conducted at the University of Munich by a team of internal medicine and radiology specialists found the coronary artery calcification (CAC) score to be a significant prognostic indicator based on 109 SARS-CoV-2-infected patients. Authors found the median CAC to be 140 [IQR 1–1165] in patients with critical COVID-19, and 160 [IQR: 88–562] in patients with fatal outcome. Authors note limitations due to retrospective design and small sample size, however, these findings suggest that coronary artery disease is significantly associated with an adverse clinical outcome in COVID-19.

· Oxygen saturation/fraction of inhaled oxygen is associated with mortality in patients with COVID-19 associated pneumonia requiring oxygen therapy. A retrospective cohort study from a group of South Korean Internists analyzed 59 hospitalized COVID-19 patients in hypoxic respiratory failure , and found that the SpO2:FiO2 (SF ratio) was predictive of ARDS occurrence (p < .001). Results also demonstrated that the SF ratio at exacerbation (HR, 0.916; 95% CI, 0.846-0.991; P = 0.029) and National Early Warning Score (NEWS) (HR, 1.277; 95% CI, 1.010-1.615; P = 0.041) were significant predictors of mortality. These findings are clinically significant because predicting development of ARDS and mortality allows physicians to effectively triage and treat the highest risk patients. Additionally, the SF ratio has many advantages over the traditionally used P:F ratio (PaO2:FiO2) during the COVID-19 pandemic because it does not require measurement of arterial blood gas, thus conserving valuable time and resources.

Adjusting Practice During COVID-19

· There is a high prevalence of deep venous thrombosis in non-severe COVID-19 patients hospitalized for a neurovascular disease. This prospective study from Strasbourg University Hospital, France evaluates 13 patients with non-severe COVID-19 and concurrent neurovascular disease for deep venous thrombosis (DVT) via doppler ultrasound scanning (DUS) of the lower limbs. Results showed that despite thromboprophylaxis, the prevalence of asymptomatic DVT was 38.5%. The authors thus advocate for the use of bedside DUS to identify DVT in patients with COVID-19 given that D-dimer, the classic marker of DVT, has been shown to correlate with COVID-19 severity and may be elevated in this population regardless of coagulable state.

R&D: Diagnosis & Treatments

· What have we learned about viral cultures and COVID-19 infectious potential? A review, conducted at University of Oxford, analyzes 29 studies that attempted to culture SARS-CoV-2 to estimate potential or observed infectivity. The authors state an apparent correlation between length of time between specimen collection and test, cycle threshold, and symptom severity. Furthermore, they found cycle threshold to be a good surrogate for viral load as it correlated with increased infection of Vero E6 cells by SARS-CoV-2. Inconsistency in culturing methods limit study power, highlighting the need for standardization of this process.

· Inconclusive COVID-19 PCR results have high rates of false positive tests. Infectious disease physicians from UCLA analyzed inconclusive SARS-CoV-2 RT-PCR tests (18 cases from a CDC assay and 51 from the TaqPath assay) to determine rates of false positive tests and to create an algorithm to make determinations on inconclusive tests. The authors found that the rate of false positives in the inconclusive tests ranged between 14-39% and that lowering the cycle threshold cutoff from 40 to 37 in the TaqPath assay significantly lowered the false-positive rate. This study demonstrates that there is a significant rate of false positive RT-PCR SARS-CoV-2 tests, which can be corrected through additional testing and changing of cycle thresholds, though this may make false negative results more likely.

· Hydroxychloroquine with or without azithromycin was found to have no effect in mild-to-moderate COVID-19. A multicenter randomized controlled trial conducted by HCor Research Institute in Sao Paulo, Brazil across 55 hospitals in Brazil included 667 adult patients hospitalized with suspected or confirmed mild-moderate COVID-19 (receiving < 4L/min O2) with less than 14 days since symptom onset who received: standard care, standard care plus hydroxychloroquine 400 mg twice daily, or standard care plus hydroxychloroquine 400 mg twice daily plus azithromycin 500 mg once daily for 7 days. It was determined that a higher ordinal score (worse prognosis) at 15 days was not affected by hydroxychloroquine or hydroxychloroquine plus azithromycin treatment and did not change with amount of time since randomization. This suggests use of hydroxychloroquine, with or without azithromycin, in mild-to-moderate COVID-19 infection has no effect on improving clinical status at 15 days compared to standard care.


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