Use of convalescent plasma therapy in eight individuals with mild COVID-19.

Coronavirus disease 2019 (COVID-19) is still a global epidemic. Several studies of individuals with severe COVID-19 regard convalescent plasma (CP) transfusion as an effective therapy. However, no significant improvements are found in randomized clinical trials of CP treatment. Until now, data for individuals with mild COVID-19 transfused CP were lacking. This study recruited eight individuals with mild COVID-19 who received at least one dose of CP transfusion. After CP therapy, the clinical symptoms of all individuals improved. Lymphocyte counts tended to increase, and lactate dehydrogenase, creatine kinase and aspartate aminotransferase tended to decrease. However, C-reactive protein increased transiently in three individuals. The median time for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test to become negative was 2.5 days after CP transfusion. The study shows the potential benefits of CP. Meanwhile, CP probably enhances the inflammatory response to SARS-CoV-2 temporarily in people with insufficient antiviral immunity. However, the effects of CP are not permanent.

Spatial orientation of the vestibular system: dependence of optokinetic after-nystagmus on gravity.

1. Monkeys received optokinetic stimulation at 60 degrees/s about their yaw (animal vertical) and pitch (animal horizontal) axes, as well as about other head-centered axes in the coronal plane. The animals were upright or tilted in right-side-down positions with regard to gravity. The stimuli induced horizontal, vertical, and oblique optokinetic nystagmus (OKN). OKN was followed by optokinetic after-nystagmus (OKAN), which was recorded in darkness. 2. When monkeys were tilted, stimulation that generated horizontal or yaw axis eye velocity during OKN induced a vertical or pitch component of slow phase velocity during OKAN. This has been designated as "cross-coupling" of OKAN. Eigenvalues and eigenvectors associated with the system generating OKAN were found as a function of tilt. They were determined by use of the Levenberg-Marquardt algorithm to minimize the mean square error between the output of a model of OKAN and the data. 3. The eigenvector associated with yaw OKAN (yaw axis eigenvector) was maintained close to the spatial vertical regardless of the angle of tilt. The eigenvector associated with pitch OKAN (pitch axis eigenvector) was always aligned with the body axis. The data indicate that velocity storage can be modeled by a piecewise linear system, the structure of which is dependent on gravity and the yaw axis eigenvector, which tends to align with gravity. 4. Yaw axis eigenvectors were also determined by giving optokinetic stimulation about head-centered axes in the coronal plane with the animal in various angles of tilt. A technique using a spectral analysis of residuals was developed to estimate whether yaw and pitch OKAN slow phase velocities decayed concurrently at the same relative rate and over the same time course. The eigenvectors determined by this method were in agreement with those obtained by analyzing OKAN elicited by yaw OKN. 5. During yaw OKN with the animal in tilted positions, the mean vector of the ensuing nystagmus was closer to the body axis than to the spatial vertical. This suggests that there is suppression of the cross-coupled pitch component during OKN. The direction of the stimulus may be utilized to suppress components of velocity storage not coincident with the direction of stimulus motion. 6. There were similarities between the monkey eigenvectors and human perception of the spatial vertical, and the mean of eigenvectors for upward and downward eye velocities overlay human 1-g perceptual data.(ABSTRACT TRUNCATED AT 400 WORDS)

The acute effects of unilateral vestibular neurectomy on sensory and motor tests of human otolithic function.

Patients were tested 1 day before and 1 week after therapeutic unilateral vestibular neurectomy (UVN) on vestibular tests which are likely determined primarily by otolithic function. UVN causes a maintained ocular torsion: fundus photographs showed that both eyes of every patients were rolled such that the upper pole of both eyes was tonically deviated towards the operated side, and there is a corresponding change in the perceived gravitational horizontal: patients set a small bar of LEDs bar down on the same side as their operation. One week after UVN, patients showed an asymmetrical sensitivity to linear acceleration vectors directed along their interaural axis in comparison to their preoperative settings for the same stimuli.

Human ocular torsional position before and after unilateral vestibular neurectomy.

The static ocular torsional position of both eyes of 23 patients was measured by means of fundus photographs one day before and one week after unilateral vestibular neurectomy for the treatment of acoustic neuroma, Ménière's disease or paroxysmal vertigo. The results showed that in all patients the vestibular neurectomy caused both eyes to tort (i.e. to roll around the visual axis) toward the side of the neurectomy when measured one week after operation. The extent of this torsion was an average of 9.5 degrees one week after operation and there was no statistically significant difference in the average magnitude of the torsion in the two eyes. In 8 of these patients, additional measurements were made at intervals up to one year after operation and it was found that in these patients there is a significant reduction in torsion over time from an average of 10.2 degrees one week after operation to an average of 2.8 degrees by 16 weeks after operation. The change in torsional eye position following the neurectomy was accompanied by a change in the perceived visual orientation of a small (9.5 degrees visual angle) illuminated horizontal line at a straight ahead eye level position in an otherwise completely darkened room. One week after operation when asked to adjust the line to the perceived gravitational horizontal by rotating it in roll (i.e. around an X axis), patients who had had a right vestibular neurectomy consistently set the line so that the right side of the line (from the patient's point of view) was below the true gravitational horizontal. Similarly patients after a left neurectomy consistently set the line so that the left side of the line was below the true gravitational horizontal. There is a high correlation (r = 0.95) between the direction and magnitude of the change in torsional eye position and the direction and magnitude of the change in the perceived visual horizontal one week after operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis of unilateral otolith hypofunction.

Asymmetric vestibular function is the basis of vertigo. Whereas caloric tests can identify unilateral peripheral loss or impairment of horizontal semicircular canal function reasonably accurately, there is as yet no single accepted test of unilateral otolith hypofunction. In some advanced vestibular laboratories around the world, new and perhaps diagnostically useful tests of otolith function are being devised. The physiologic basis and the present clinical applications of these tests are reviewed.

Human otolithic function before and after unilateral vestibular neurectomy.

One index of otolith function is the so-called oculogravic "illusion" that during centrifugal stimulation a small luminous bar, fixed with respect to the observer, appears to be roll-tilted by the same amount that the observer feels to be roll-tilted. Many patients undergoing therapeutic unilateral vestibular nerve section show the illusion symmetrically for left and right roll-tilts prior to the operation, but at testing one week after vestibular nerve section show a large asymmetry: they perceive the illusion when the resultant force is directed toward their intact ear, but they perceive a much reduced illusion when the force is directed toward their operated ear. This roll-tilt perceptual response asymmetry appears similar to the asymmetrical horizontal semicircular canal vestibulo-ocular responses for symmetrical but opposite head accelerations that these same patients exhibit for values of head angular accelerations in the natural range (Ewald's second law), and the present paper suggests that a version of Ewald's second law may apply to the otolithic system: specifically, that there is a response asymmetry for linear accelerations. Anatomical and physiological evidence concerning such an otolithic asymmetry is reviewed.

Linear acceleration perception in the roll plane before and after unilateral vestibular neurectomy.

The ability of 33 patients to perceive the direction, relative to the body long axis, of a linear acceleration vector acting in the coronal plane, roll-tilt perception, was studied at various times, before and from 1 week to 6 months after unilateral, selective vestibular neurectomy for Meniere's disease, acoustic neuroma or intractable paroxysmal vertigo. The results of these patients were compared with the results of 31 normal subjects and two control patients who had both vestibular nerves surgically sectioned. Rotating on a fixed-chair centrifuge in an otherwise darkened room, each observer was required to indicate his perception of the direction of the resultant gravito-inertial vector by setting a small, motor-driven, illuminated bar, attached to the chair but rotatable in the fronto-parallel plane, to the perceived gravitational horizontal. Normal subjects accurately align the bar with respect to the gravito-inertial resultant vector which, in the dark, they assume to be the gravitational vertical. This percept has been called the oculogravic illusion. Accurate roll-tilt perception is due to vestibular (probably mainly otolithic) sensory information since patients with bilateral vestibular neurectomies do not perceive the resultant vector accurately. Whereas normal subjects perceive resultant vectors directed to the right and to the left equally accurately, roll-tilt perception was invariably asymmetrical one week after unilateral vestibular neurectomy. Even at rest there was an asymmetry in the baseline settings, so that patients set the bar down on the side of the operated ear, in order for it to appear gravitationally horizontal: if a patient had a right vestibular nerve section then he set the bar clockwise (from the patient's view) below the true gravitational horizontal. With increasing gravito-inertial resultant angles there was an increasing asymmetry of roll-tilt perception due both to decreased sensitivity to roll-tilt stimuli directed towards the operated ear and to transiently increased sensitivity to roll-tilt stimuli directed towards the intact ear. A progressive decrease in both perceptual asymmetries followed, rapidly in the first 3 weeks, more slowly in the next 6 months.(ABSTRACT TRUNCATED AT 400 WORDS)

A model of otolith stimulation.

A new model of otolithic stimulation by linear acceleration is presented and compared to previous models, based upon anatomical evidence and on the ability of normal subjects to sense the direction of a linear acceleration vector acting in the coronal plane (roll-tilt perception). There are two basic methods of generating roll-tilt stimuli: 1) tilt-chairs either inside or outside a centrifuge and 2) fixed-chair centrifuges. The present model is based on consideration of the probable otoconial displacement produced by these two different methods of stimulation and the model incorporates a major role for the elastic restoring force of the otolith membrane. When this force is taken into account, and most previous models have ignored it, the model predicts that different patterns of otoconial displacement will be produced in tilt-chair and in fixed-chair centrifuge experiments. The different roll-tilt perception produced by these two methods may be caused by the different otoconial displacement patterns. It is suggested that the elastic restoring force of the otoconial membrane may contribute to space motion sickness.