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December 30 | Daily COVID-19 LST Report

Climate

· The US Centers for Disease Control COVID-19 Response Team used data from three online CARAVAN omnibus surveys (n=858) conducted to assess parental attitudes and concerns about schools reopening during the COVID-19 pandemic and found more white families were in favor of in-person school (62.3%) compared to Hispanic families (50.2%, p=0.014) and Black families (46.0%, p=0.007), while non-white parents were more concerned about schools opening safely (98.8% very or somewhat concerned) than were white families (86.0%, p=0.012). Authors suggest socioeconomic differences and structural inequities may drive these differing attitudes and recommend school districts consider each community's unique needs when devising school reopening plans.


Epidemiology

· In a retrospective cohort study evaluating albumin levels in correlation with disease severity and inflammatory markers (CRP, d-dimer, and IL-6), investigators in Milan, Italy analyzed data from 207 COVID-19 patients admitted to Fatebenefratelli-Sacco Hospital and found 50.7% patients had hypoalbuminemia (serum albumin <30 g/L), and that albumin levels were significantly inversely correlated with increased severity of disease and worse outcomes at day 30, as well as inversely correlated with inflammatory markers. The results suggest hypoalbuminemia and urinary protein wasting may be useful biomarkers on admission to determine disease severity.

· A cohort study by an international team of researchers compares COVID-19 outcomes in pregnant women (n=1549) vs non-pregnant women of reproductive age (n=19,825) from the Mexican National Registry of Coronavirus database and found that pregnant women had higher odds of death (OR 1·65, 95% CI 1·30-2.09), pneumonia (OR 1·99, 95% CI 1·81-2·19) and ICU admission (OR 2.25, 95% CI 1·86-2·71) than non-pregnant women, but similar odds of intubation (OR 0·93, 95% CI 0·70-1·25). Authors note additional research is required to understand potential mechanisms of this increased risk, and determine the external validity of this cohort of patients.

Understanding the Pathology

· Microbiologists and infectious disease specialists from Anhui Medical University and the Anhui and Fuyang Centers for Disease Control in China analyzed SARS-CoV-2 IgM and IgG antibody responses using indirect ELISA in serum from 165 patients and found spike protein IgM and IgG was detectable in 12.5% of hospitalized patients on day 1 of infection, IgM peaked at 22-28 days and was undetectable in 30% and 79% of patients at three and seven months, respectively, and IgG peaked at four months and declined rapidly at seven months. Authors suggest their analysis can help guide SARS-CoV-2 diagnosis and vaccine development via an improved understanding of the human humoral response in COVID-19.

Transmission & Prevention

· A review of current data on COVID-19 transmission and vaccine efficacy by otolaryngologists from Harvard Medical School and Johns Hopkins School of Medicine illustrates how COVID-19 mRNA vaccines generate immunogenicity by creating IgG antibodies against the SARS-CoV-2 virus, however IgG antibodies, while preventing patients from clinically getting sick with COVID-19, do not stop the virus from replicating in the upper airway -- as this requires secretory IgA antibodies -- suggesting that transmission precautions should still be widely practiced even after vaccination.

· An international group of researchers discuss possible explanations for why the household secondary attack rates (HSAR) in Asian countries such as Singapore and China (12% and 11% respectively) are significantly lower than in the US (30-50%). Authors attribute this difference to self-isolation protocols in Asia, such as the Chinese "fangcang shelter hospitals," which provide COVID-19 positive individuals with a healthcare facility where they can quarantine until no longer infectious. Conversely, the strategy in the US and Europe centers around home quarantining, leading to higher rates of secondary infections. While significant cultural and structural differences exist that would prevent the US from successfully implementing a similar self-isolation protocol to those seen in the Asian countries highlighted, further research is needed to identify areas for improvement in current US public health policies.


Management

· A multicenter retrospective study conducted by French physicians at the Cochin Hospital utilized demographic data, clinical symptomatology, and results of lab tests from 605 patients with clinical suspicion of COVID-19 to create a pre-test probability score of SARS-CoV-2 infection (the PARIS score) and found that fever, myalgias, lymphopenia, and elevated CRP had the highest positive predictive value, though no clinical variable was individually significant. The high-probability PARIS score had a positive predictive value of 93%, while the low-probability score had a negative predictive value of 98%. This study adds to the existing body of evidence by providing an evidenced-based prediction tool that can easily be incorporated into clinical practice, however further external validation is still needed.

· A systematic review by South Korean radiologists found the incidence of pulmonary embolism (PE) and deep vein thrombosis (DVT) in patients with COVID-19 were 16.5% and 14.8% respectively, and that only 42% of PE patients had evidence of DVT. Additionally, data revealed that D-dimer levels of 500 and 1000 micrograms/L showed high sensitivity (96% and 91%, respectively) but low specificity (10% and 24%) for detecting PE. These findings suggest that coagulopathy in COVID-19 may be more severe than typical illness (estimated rates of PE and DVT in critically-ill hospitalized patients 6-10%) and possibly occur via a distinct mechanism of localized endothelialitis instead of lower extremity DVT.

R&D: Diagnosis & Treatments

· This industry-sponsored phase 3 randomized controlled trial involving 389 hospitalized patients with COVID-19 pneumonia found that patients who received IV tocilizumab had faster recovery rates and less chance of progression to mechanical ventilation or death after 28 days compared to the placebo group (12% vs 19.3%, hazard ratio 0.56, 95% CI 0.33-0.97, p=0.04), suggesting that this IL-6 inhibitor may be an effective treatment to reduce hospital days and ventilator use in COVID-19. Importantly, this trial was conducted in 6 countries and included over 80% minority populations, who are known to have disproportionately worse outcomes and less inclusion in clinical trials compared to their white counterparts. However, there was no significant difference in overall all-cause mortality, and the current cost of this brand name biologic may be prohibitive for wide scale use in these populations.

· A group of hematology and immunology experts illustrate how SARS-CoV-2 directed T-cell immunotherapy may be a feasible method for prevention and early treatment of COVID-19 in immunocompromised patients by demonstrating how in-vitro expansion of SARS-CoV-2 specific T-cells in convalescent plasma donors can be directed to recognize and elicit a robust T-cell immune response to common viral antigens. Specifically, they found increased interferon-γ production (representative of "polyfunctional T-cell response") to SARS-CoV-2 spike protein, membrane protein, and nucleocapsid peptide in 12 (26%), 27 (59%), and 10 (22%) convalescent donors (respectively), as well as in 2 of 15 unexposed controls. The authors propose that this adaptive immune response is critical for developing effective long-term immunity, and may be beneficial for immunocompromised patients with blood disorders or bone marrow transplants.

Mental Health & Resilience Needs

· Scientists from the Center for Disease Control studied emergency department (ED) visits from January 6, 2019 - September 6, 2020 and found an increase in the proportion of ED visits related to abuse and neglect in children and adolescents during the COVID-19 pandemic despite a lower number of ED visits overall, and those visits were more likely to result in hospitalization than in 2019. This suggests that the social and economic effects of the pandemic (loss of income and increased stress related to parental child care, increased substance use, and mental health conditions) may be the cause of this increase, and the authors suggest strengthening families’ economic support, ensuring family-friendly work policies, and modifying early home visitation practices to improve the safety of children and adolescents.

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