BackgroundAn association between the severity of COVID-19 and the presence of certain chronic conditions has been suggested. However, unlike influenza and other viruses, the disease burden in patients with asthma has been less evident.ObjectiveTo understand the impact of COVID-19 in patients with asthma.MethodsUsing big data analytics and artificial intelligence through the SAVANA Manager® clinical platform, we analysed clinical data from patients with asthma from January 1st to May 10th, 2020.ResultsOut of 71 182 patients with asthma, 1006 (1.41%) suffered from COVID-19. Compared to asthmatic individuals without COVID-19, patients with asthma and COVID-19 were significantly older (55 versus 42 years), predominantly female (66% versus 59%), smoked more frequently, and had higher prevalence of hypertension, dyslipidemias, diabetes, and obesity. Allergy-related factors such as rhinitis and eczema were less common in asthmatic patients with COVID-19 (p<.001). Higher prevalence of these comorbidities was also observed in patients with COVID-19 who required hospital admission. The use of inhaled corticosteroids (ICS) was lower in patients who required hospitalisation due to COVID-19, as compared to non-hospitalised patients (48.3% versus 61.5%; OR: 0.58: 95% CI 0.44–0.77). Although patients treated with biologics (n=865; 1.21%) showed increased severity and more comorbidities at the ENT level, COVID-19-related hospitalisations in these patients were relatively low (0.23%).ConclusionPatients with asthma and COVID-19 were older and at increased risk due to comorbidity-related factors. ICS and biologics are generally safe and may be associated with a protective effect against severe COVID-19 infection.

SUMMARY The nervous systems of diverse species, including worms and humans, possess mechanisms for distinguishing between sensations arising from self-generated (i.e., expected) movements from those arising from other-generated (i.e., unexpected) movements [1–3]. To make this critical distinction, animals generate copies, or corollary discharges, of motor commands [4, 5]. Corollary discharge facilitates the selective gating of reafferent signals arising from self-generated movements, thereby enhancing detection of novel stimuli [6–10]. However, for a developing nervous system, such sensory gating would be counterproductive if it impedes transmission of the very activity upon which activity-dependent mechanisms depend [11]. In infant rats during active (or REM) sleep—a behavioral state that predominates in early infancy [12–16]—neural circuits within the brainstem [17, 18] trigger hundreds of thousands of myoclonic twitches each day [19]. The putative contribution of these self-generated movements to the activity-dependent development of the sensorimotor system is supported by the observation that reafference from twitching limbs reliably and substantially triggers brain activity [20–23]. In contrast, under identical testing conditions, even the most vigorous wake movements reliably fail to trigger reafferent brain activity [21–23]. One hypothesis that accounts for this paradox is that twitches, uniquely among self-generated movements, lack corollary discharge [23]. Here, we test this hypothesis in newborn rats by manipulating the degree to which self-generated movements are expected and, therefore, their presumed recruitment of corollary discharge. We show that twitches, although self-generated, are processed as if they are unexpected.

Summary Neuronal oscillations comprise a fundamental mechanism by which distant neural structures establish and express functional connectivity. Long-range functional connectivity between the hippocampus and other forebrain structures is enabled by theta oscillations. Here we show for the first time that the infant rat red nucleus (RN)—a brainstem sensorimotor structure— exhibits theta (4-7 Hz) oscillations restricted primarily to periods of active (REM) sleep. At postnatal day (P) 8, theta is expressed as brief bursts immediately following myoclonic twitches; by P12, theta oscillations are expressed continuously across bouts of active sleep. Simultaneous recordings from the hippocampus and RN at P12 show that theta oscillations in both structures are coherent, co-modulated, and mutually interactive during active sleep. Critically, at P12, inactivation of the medial septum eliminates theta in both structures. The developmental emergence of theta-dependent functional coupling between the hippocampus and RN parallels that between the hippocampus and prefrontal cortex. Accordingly, disruptions in the early expression of theta could underlie the cognitive and sensorimotor deficits associated with neurodevelopmental disorders such as autism and schizophrenia.

Sensory feedback from sleep-related myoclonic twitches is thought to drive activity-dependent development in spinal cord and brain. However, little is known about the neural pathways involved in the generation of twitches early in development. The red nucleus (RN), source of the rubrospinal tract, has been implicated in the production of phasic motor activity during active sleep in adults. Here we hypothesized that the RN is also a major source of motor output for twitching in early infancy, a period when twitching is an especially abundant motor behavior. We recorded extracellular neural activity in the RN during sleep and wakefulness in 1-week-old unanesthetized rats. Neurons in the RN fired phasically before twitching and wake movements of the contralateral forelimb. A subpopulation of neurons in the RN exhibited a significant peak of activity after forelimb movement onset, suggesting reafferent sensory processing. Consistent with this observation, manual stimulation of the forelimb evoked RN responses. Unilateral inactivation of the RN using a mixture comprising GABA A , GABA B , and glycine receptor agonists caused an immediate and temporary increase in motor activity followed by a marked and prolonged decrease in twitching and wake movements. Altogether, these data support a causal role for the RN in infant motor behavior. Furthermore, they indicate that twitching, which is characterized by discrete motor output and reafferent input, provides an opportunity for sensorimotor integration and activity-dependent development of topography within the newborn RN.

Active sleep (AS) provides a unique developmental context for synchronizing neural activity within and between cortical and subcortical structures. In week-old rats, sensory feedback from myoclonic twitches, the phasic motor activity that characterizes AS, promotes coherent theta oscillations (4–8 Hz) in the hippocampus and red nucleus, a midbrain motor structure. Sensory feedback from twitches also triggers rhythmic activity in sensorimotor cortex in the form of spindle bursts, which are brief oscillatory events composed of rhythmic components in the theta, alpha/beta (8–20 Hz), and beta2 (20–30 Hz) bands. Here we ask whether one or more of these spindle-burst components are communicated from sensorimotor cortex to hippocampus. By recording simultaneously from whisker barrel cortex and dorsal hippocampus in 8-day-old rats, we show that AS, but not other behavioral states, promotes cortico-hippocampal coherence specifically in the beta2 band. By cutting the infraorbital nerve to prevent the conveyance of sensory feedback from whisker twitches, cortical-hippocampal beta2 coherence during AS was substantially reduced. These results demonstrate the necessity of sensory input, particularly during AS, for coordinating rhythmic activity between these two developing forebrain structures.