March 21, 2024

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COVID: Cytokine Storm Week

Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19: The HOT-COVID Randomized Clinical Trial
These are the results of a multicenter randomized trial where 726 patients in 11 ICUs in Europe with COVID-19 and severe hypoxemia were randomized to different targets. At 90 days, the median time alive without life support was 80.0 days in the lower-oxygenation group and 72.0 days in the higher-oxygenation group. Death rate at 90 days was 30.2% in the lower-oxygenation group and 34.7% in the higher-oxygenation group (risk ratio, 0.86; 98.6% confidence interval, 0.66 to 1.13). In an editorial on the study, Oxygen Supplementation in COVID-19 — How Much Is Enough? Richard M. Schwartzstein, MD, of Harvard Medical School, writes that the less-is-more findings could be explained by a number of factors. More patients in the high-target group could have been intubated and started on mechanical ventilation because physicians could not achieve the target with noninvasive ventilation. "The observation that initiation of mechanical ventilation to achieve a high target Pao2 may have occurred is less a failing of the study design than a consequence of using a high Pao2 target," Schwartzstein writes.

COVID: The Late Phase/PASC/Long COVID

Prevalence of Orthostatic Intolerance in Long COVID Clinic Patients and Healthy Volunteers: A Multicenter Study
The authors investigated the prevalence of objective orthostatic intolerance (OI) in patients attending Long COVID clinics and healthy volunteers. They also looked at associations with OI symptoms and comorbidities. Participants with a diagnosis of Long COVID were recruited from eight UK Long COVID clinics, and healthy volunteers from general population. All undertook standardized National Aeronautics and Space Administration Lean Test (NLT). Participants' history of typical OI symptoms (e.g., dizziness, palpitations) before and during the NLT were recorded. Two hundred seventy-seven Long Covid patients and 50 frequency-matched healthy volunteers were tested. Healthy volunteers had no history of OI symptoms or symptoms during NLT or PoTS, 10% had asymptomatic orthostatic hypotension (OH). One hundred thirty (47%) Long COVID patients had previous history of OI symptoms and 144 (52%) developed symptoms during the NLT. Forty-one (15%) had an abnormal NLT, 20 (7%) met criteria for PoTS, and 21 (8%) had OH. Of patients with an abnormal NLT, 45% had no prior symptoms of OI. Relaxing the diagnostic thresholds for PoTS from two consecutive abnormal readings to one abnormal reading during the NLT, resulted in 11% of Long COVID participants (an additional 4%) meeting criteria for PoTS, but not in healthy volunteers. More than half of Long COVID patients experienced OI symptoms during NLT and more than one in 10 patients met the criteria for either PoTS or OH, half of whom did not report previous typical OI symptoms. The investigators conclude by recommending that all patients attending Long COVID clinics are offered an NLT and appropriate management commenced.
Autonomic Cardiac Function in Children and Adolescents with Long COVID: A Case-controlled Study
While prior studies focused on autonomic dysfunction have primarily been conducted in adults, in this study, the authors assessed whether pediatric patients with Long COVID present abnormalities in autonomic cardiac function. Fifty-six Long COVID pediatric patients (mean age 10.3 ± 3.8 y) and 27 age-, sex-, and body surface area-matched healthy controls (mean age 10.4 ± 4.5y) underwent a standard 12-lead electrocardiography (ECG) and 24-h ECG Holter monitoring. Autonomic cardiac function was assessed. A comprehensive echocardiographic study was also obtained by two-dimensional echocardiography and tissue Doppler imaging. Data analysis showed that pediatric patients with Long COVID had significant changes.
Iron Dysregulation and Inflammatory Stress Erythropoiesis Associates with Long-term Outcome of COVID-19
In this investigation that assessed 214 individuals infected with SARS-CoV-2, with varying disease severity they found unresolving inflammation, anemia, low serum iron, altered iron-homeostasis gene expression. Really, an anemia of chronic inflammation. Noted in a related University of Cambridge Research editorial post: “When the body has an infection, it responds by removing iron from the bloodstream. This protects us from potentially lethal bacteria that capture the iron in the bloodstream and grow rapidly. It’s an evolutionary response that redistributes iron in the body, and the blood plasma becomes an iron desert. It isn't necessarily the case that individuals don't have enough iron in their body, it's just that it’s trapped in the wrong place. What we need is a way to remobilize the iron and pull it back into the bloodstream, where it becomes more useful to the red blood cells.” So we do not know if iron supplementation is helpful but this study does not tell us the answer.