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June 24 | Daily COVID-19 LST Report

Climate

· The director of the World Health Organization Collaborating Center on Public Health Law and Human Rights recommend using the current COVID-19 pandemic to rebuild the World Health Organization (WHO) as a more responsive international agency by:

o allocating more funding

o ensuring member state compliance with WHO's recommendations

o increasing WHO's freedom to act without political influence.

· Researchers in Ahmedabad, India predict that this will affect 26 million couples in India and result in 2.4 million unintended pregnancies, 1.45 million abortions, and 1,700 maternal deaths.

o Lack of PPE, interruption of public transport, and reallocation of healthcare workers to treatment of COVID-19 patients has led to a decrease in provision of:

§ injectable contraceptives (down 36%),

§ abortions (down 28%),

§ condom kits (down 23%),

§ IUD insertion (down 21%),

§ oral contraceptives (down 15%).

· Approximately 33% of rural counties, 29% of semi-rural counties, and 19% of micropolitan counties fall into the high-risk category based on 11 susceptibility and resiliency indicators created by an author at Iowa State University. This was thought to be a result of lack of health care, social services, and high-speed internet access, making telemedicine nearly impossible. Thus, the author suggests that many rural and semi-rural communities may be underprepared for a COVID-19 outbreak.




Epidemiology

· Descriptive analyses conducted by researchers affiliated with the Centers for Disease Control (CDC) COVID-19 Emergency Response assessed the demographic characteristics, underlying health conditions, symptoms, and outcomes of 1,320,488 confirmed United States cases of COVID-19 from January 22 to May 30, 2020 (Figure). Their results depict the state of the ongoing public health crisis due to COVID-19 and highlight the need for mitigation strategies to slow transmission, especially for vulnerable populations.

o Major findings included:

§ The cumulative incidence was 403.6 cases per 100,000 persons, incidence was similar between males and females, and the highest incidence was in persons aged 80 year or older at 902 per 100,000 persons.

§ Among positive cases that reported race and ethnicity, 33% were Hispanic patients, 22% were black, and 1.3% were American Indian or Alaska Native, suggesting that these groups were disproportionately affected by COVID-19.

§ Among cases that reported underlying health conditions, 32% of COVID-19 patients had cardiovascular disease, 30% had diabetes, and 18% had chronic lung disease.

§ Hospitalizations and deaths were higher in patients with reported underlying health conditions.

Understanding the pathology

· A single-cell RNA sequencing (scRNAseq) study conducted in multiple centers in Shanghai, China focused on the expression of ACE2 as a model for SARS-CoV-2 virulence and found:

o ACE2 was expressed in arterial vascular cells of fibrotic lungs (compared to alveolar type 2 [AT2] cells of normal lungs), which authors suggest may allow the virus to spread hematogenously by transporting across the lung-blood interface.

o Both TMPRSS2 and FURIN were expressed in AT2 cells of normal lungs, but only FURIN was found in fibrotic lungs, suggesting that FURIN alone is sufficient for SARS-CoV-2 viral entry into cells of fibrotic lungs.

o Higher ACE2-positive rates in failed heart cells, which authors suggest may allow the virus to spread to the heart from the lungs and play a role in multi-organ involvement and cardiac injury.

o Lower ACE2 expression in arterial vascular cells of failed hearts, which could correlate with weak infectability of the heart.

o Normal hearts showed expression of viral response genes compared to failed hearts which expressed more inflammatory markers.

o ACE2 lung expression in human carcinoma and mice tissue was upregulated in response to viral infection and LPS inflammation, respectively, suggesting that previous viral infection or inflammatory states may make patients more susceptible to COVID-19.

Management

· Obstetricians at four academic medical centers in New York City found significant changes to their labor and delivery policies when mothers were known or suspected to have COVID-19.

· Notable changes included the following:

o Requiring staff to wear surgical masks.

o Screening patients for COVID-19 using history and temperature.

o Performing deliveries in a negative pressure room when available.

o Medication usage: most of the sites reported using corticosteroids for fetal lung maturity, magnesium sulfate for COVID-19 patients experiencing preterm labor or preeclampsia, and no use of carboprost.

o Thromboprophylaxis was initiated at three of the four sites (rationale for this was not stated, but was likely due to presumed increased risk in COVID-19).

o There were significant differences in the sites' policies for checking the fetus in a hospitalized pregnant patient who tested positive for SARS-CoV-2, with one site starting to check a daily fetal heartbeat at 24 weeks and another site starting at 34 weeks. Half the sites performed daily non-stress tests in addition to fetal heartbeat checks.

Adjusting the practice

· COVID-19 pandemic to include strategies to help patients' families cope with being separated from their loved ones during ICU stays and potentially end-of-life processes.

· The authors specifically say that ICU providers must:

o acknowledge the uniqueness of the situation with families,

o initiate video conferencing early in treatment when possible and if desired by the family,

o allow themselves to display their emotions when talking with families, and

o address potential mental health issues and trauma responses directly.

· Authors from the Washington University in St. Louis School of Medicine and Mayo Clinic in Rochester recommend the following:

o A combination of all of these should be considered the "Gold Standard" for this diagnosis (Table 2).

§ Known exposure history.

§ Symptoms and clinical exam:

§ Fever is the most common symptom of COVID-19 seen in 84%-87%.

§ Hyposmia ([LR+] 5.3, [LR-] 0.61) and hypogeusia (LR+ 7.1, LR- 0.38) are better to rule-in COVID-19; less helpful to rule out.

§ Routine Labs: -Lymphopenia is seen in over 50% of COVID-19 patients. -Elevated prothrombin time, ferritin, D-dimer, or IL-6 seen in severe COVID-19.

§ Imaging: -Single view Chest X-ray has sensitivity range from 33-60%. -CT may increase diagnostic sensitivity in conjunction with rRT-PCR; ~97% sensitivity.

§ Serology: -May identify past SARS-CoV-2 infection. -High false-positive rate; test specificity ranges 87-100%.

§ Viral culture with rRT-PCR (real-time RT-PCR): -rRT-PCR is the standard criterion for diagnosis. -High false-negativity rate; test sensitivity ranges 60-78% (Table 1 for common causes). -Blood and urine samples for rRT-PCR are inadequate due to limited virus in body fluids.

R&D Diagnosis and Treatments

· This retrospective case-control study conducted at Maimonides Medical Center, New York evaluates mortality differences in severe and critical COVID-19 patients treated with tocilizumab, an interleukin-6 inhibitor. While there was no significant difference in mortality between the tocilizumab-treated cohort (n=96) and the control patients (n=97; 52% vs. 62.1% P= 0.09), exclusion of intubated patients revealed a significantly decreased mortality rate in the treated cohort (6% vs. 27% P= 0.024; Table 3). Given limitations in exact matching of the cohorts, the authors urge for randomized control trials to evaluate tocilizumab’s role in controlling the cytokine storm linked to high mortality in COVID-19 patients.

· Iranian authors performed a review of in vivo and in vitro studies from the last 50 years to document Ivermectin's antiviral activities against a wide variety of DNA and RNA viruses, including SARS-CoV-2 (Table 1). Although an in vitro study has shown Ivermectin's antiviral activity against COVID-19, the authors warn against immediately using Ivermectin as a therapy, which is consistent with Food and Drug Administration (FDA) recommendations as well; the lack of in vivo studies available support the need for more clinical trials and safer formulations of Ivermectin prior to its establishment as a treatment for COVID-19.

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