Case Series: Evidence of Borderzone Ischemia in Critically-Ill COVID-19 Patients Who "Do Not Wake Up".

This article describes the clinical course, radiological findings, and outcome of two patients with the novel 2019 coronavirus disease (COVID-19) who remained comatose for a prolonged duration following discontinuation of all sedation. These two male patients, one aged 59-years and another aged 53-years, both with a history of hypertension and neurologically intact on admission, developed worsening COVID-19 associated acute respiratory distress syndrome (ARDS). Both required benzodiazepine, opioid, neuromuscular blockade, therapeutic anticoagulation, and vasopressor infusions in addition to renal replacement therapy. Echocardiography demonstrated normal chamber size and systolic function in both cases. Each patient demonstrated only trace flexion to pain 7-10 days following discontinuation of all sedation. Magnetic Resonance Imaging on both patients demonstrated multifocal lesions on diffusion weighted imaging with apparent diffusion coefficient correlate in bilateral middle/anterior cerebral artery borderzones, and no large-vessel occlusion or severe stenosis. In both patients, continuous electroencephalography demonstrated no seizures. Neither patient had any documented period of sustained hypotension (mean arterial pressure <60 mmHg) or hypoxia (SpO2 <90%). Ninety days following initial presentation, the 59-years-old man was oriented, with fluent speech and able to ambulate with assistance, while the other 53-years-old man was at home and independent, undertaking the basic activities required by daily living. We conclude that critically-ill COVID-19 patients with prolonged coma following sedation discontinuation may demonstrate imaging features of ischemic injury in borderzone regions despite the absence of documented sustained hypotension or hypoxia. However, substantial neurological recovery is possible despite these findings.

HIV Infection and Bone Abnormalities.

More than 36 million people are living with human immunodeficiency virus (HIV) infection worldwide and 50% of them have access to antiretroviral therapy (ART). While recent advances in HIV therapy have reduced the viral load, restored CD4 T cell counts and decreased opportunistic infections, several bone-related abnormalities such as low bone mineral density (BMD), osteoporosis, osteopenia, osteomalacia and fractures have emerged in HIV-infected individuals. Of all classes of antiretroviral agents, HIV protease inhibitors used in ART combination showed a higher frequency of osteopenia, osteoporosis and low BMD in HIV-infected patients. Although the mechanisms of HIV and/or ART associated bone abnormalities are not known, it is believed that the damage is caused by a complex interaction of T lymphocytes with osteoclasts and osteoblasts, likely influenced by both HIV and ART. In addition, infection of osteoclasts and bone marrow stromal cells by HIV, including HIV Gp120 induced apoptosis of osteoblasts and release of proinflammatory cytokines have been implicated in impairment of bone development and maturation. Several of the newer antiretroviral agents currently used in ART combination, including the widely used tenofovir in different formulations show relative adverse effects on BMD. In this context, switching the HIV-regimen from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) showed improvement in BMD of HIV-infected patients. In addition, inclusion of integrase inhibitor in ART combination is associated with improved BMD in patients. Furthermore, supplementation of vitamin D and calcium with the initiation of ART may mitigate bone loss. Therefore, levels of vitamin D and calcium should be part of the evaluation of HIV-infected patients.

Features of Maternal HIV-1 Associated with Lack of Vertical Transmission.

HIV-1 is transmitted from mother-to-child (vertical transmission) at an estimated rate of approximately 30% without any antiretroviral therapy (ART). However, administration of ART during pregnancy considerably diminishes the rate of mother-to-child transmission of HIV-1, which has become a standard of perinatal care in HIV-infected pregnant females in developed countries. Moreover, a majority of children born to HIV-infected mothers are uninfected without any ART. In addition, characteristics of HIV-1 and/or cellular factors in the mothers may play a role in influencing or preventing vertical transmission. Several studies, including from our laboratory have characterized the properties of HIV-1 from infected mothers that transmitted HIV-1 to their infants (transmitting mothers) and compared with those mothers that failed to transmit HIV-1 to their infants (non-transmitting mothers) in the absence of ART. One of the striking differences observed was that the non-transmitting mothers harbored a less heterogeneous HIV-1 population than transmitting mothers in the analyzed HIV-1 regions of p17 gag, env V3, vif and vpr. The other significant and distinctive findings were that the functional domains of HIV-1 vif and vpr proteins were less conserved in non-transmitting mothers compared with transmitting mothers. Furthermore, there were differences seen in two important motifs of HIV-1 Gag p17, including conservation of QVSQNY motif and variation in KIEEEQN motif in non-transmitting mothers compared with transmitting mothers. Several of these distinguishing properties of HIV-1 in non-transmitting mothers provide insights in developing strategies for preventing HIV-1 vertical transmission.