Doppler-derived mitral deceleration time of early filling provides a simple and accurate means of estimating pulmonary capillary wedge pressure that is particularly useful in patients with a normal or normalized mitral flow velocity pattern.

Nitazoxanide is widely available and exerts broad-spectrum antiviral activity in vitro. However, there is no evidence of its impact on SARS-CoV-2 infection.In a multicenter, randomised, double-blind, placebo-controlled trial, adult patients presenting up to 3 days after onset of Covid-19 symptoms (dry cough, fever, and/or fatigue) were enrolled. After confirmation of SARS-CoV2 infection by RT-PCR on a nasopharyngeal swab, patients were randomised 1:1 to receive either nitazoxanide (500 mg) or placebo, TID, for 5 days. The primary outcome was complete resolution of symptoms. Secondary outcomes were viral load, laboratory tests, serum biomarkers of inflammation, and hospitalisation rate. Adverse events were also assessed.From June 8 to August 20, 2020, 1575 patients were screened. Of these, 392 (198 placebo, 194 nitazoxanide) were analysed. Median time from symptom onset to first dose of study drug was 5 (4–5) days. At the 5-day study visit, symptom resolution did not differ between the nitazoxanide and placebo arms. Swabs collected were negative for SARS-CoV-2 in 29.9% of patients in the nitazoxanide arm versus 18.2% in the placebo arm (p=0.009). Viral load was also reduced after nitazoxanide compared to placebo (p=0.006). The percent viral load reduction from onset to end of therapy was higher with nitazoxanide (55%) than placebo (45%) (p=0.013). Other secondary outcomes were not significantly different. No serious adverse events were observed.In patients with mild Covid-19, symptom resolution did not differ between nitazoxanide and placebo groups after 5 days of therapy. However, early nitazoxanide therapy was safe and reduced viral load significantly.

Severe acute respiratory disease coronavirus 2 (SARS-CoV-2, formerly 2019-nCoV) is a novel coronavirus that has rapidly disseminated worldwide, causing the coronavirus disease 2019 (COVID-19) pandemic. As of January 6th, 2021, there were over 86 million global confirmed cases, and the disease has claimed over 1.87 million lives (a ∼2.2% case fatality rate). SARS-CoV-2 is able to infect human cells by binding its spike (S) protein to angiotensin-conversing enzyme 2 (ACE2), which is expressed abundantly in several cell types and tissues. ACE2 has extensive biological activities as a component of the renin-angiotensin-aldosterone system (RAAS) and plays a pivotal role as counter-regulator of angiotensin II (Ang II) activity by converting the latter to Ang (1-7). Virion binding to ACE2 for host cell entry leads to internalization of both via endocytosis, as well as activation of ADAM17/TACE, resulting in downregulation of ACE2 and loss of its protective actions in the lungs and other organs. Although COVID-19 was initially described as a purely respiratory disease, it is now known that infected individuals can rapidly progress to a multiple organ dysfunction syndrome. In fact, all human structures that express ACE2 are susceptible to SARS-CoV-2 infection and/or to the downstream effects of reduced ACE2 levels, namely systemic inflammation and injury. In this review, we aim to summarize the major features of SARS-CoV-2 biology and the current understanding of COVID-19 pathogenesis, as well as its clinical repercussions in the lung, heart, kidney, bowel, liver, and brain. We also highlight potential therapeutic targets and current global efforts to identify safe and effective therapies against this life-threatening condition.