Clinical predictors of donor antibody titre and correlation with recipient antibody response in a COVID-19 convalescent plasma clinical trial.

BACKGROUND: Convalescent plasma therapy for COVID-19 relies on transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. METHODS: Multivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed-effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. RESULTS: Donor antibody titres ranged from 0 to 1 : 3892 (anti-receptor binding domain (RBD)) and 0 to 1 : 3289 (anti-spike). Higher anti-RBD and anti-spike titres were associated with increased age, hospitalization for COVID-19, fever and absence of myalgia (all P < 0.05). Fatigue was significantly associated with anti-RBD (P = 0.03). In pairwise comparison amongst ABO blood types, AB donors had higher anti-RBD and anti-spike than O donors (P < 0.05). No toxicity was associated with plasma transfusion. Non-ECMO recipient anti-RBD antibody titre increased on average 31% per day during the first three days post-transfusion (P = 0.01) and anti-spike antibody titre by 40.3% (P = 0.02). CONCLUSION: Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titre to COVID-19. Despite variability in donor titre, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion amongst COVID-19-infected patients is needed.

Mechanical properties of the tendinous equine interosseus muscle are affected by in vivo transducer implantation.

Liquid metal strain gauges (LMSGs) were implanted in the tendinous interosseous muscle, also called suspensory ligament (SL), in the forelimbs of 6 ponies in order to quantify in vivo strains and forces. Kinematics and ground reaction forces were recorded simultaneously with LMSG signals at the walk and the trot prior to implantation, and 3 and 4 days thereafter. The ponies were euthanised and tensile and failure tests were performed on the instrumented tendons and on the tendons of the contra lateral limb, which were instrumented post mortem. The origo-insertional (OI) strain of the SL was computed from pre- and post-operative kinematics, using a 2D geometrical model. The LMSG-recorded peak strain of the SL was 5.4+/-0.9% at the walk and 9.1+/-1.3% at the trot. Failure occurred at 15.4+/-2.1% (mean+/-S.D.). The LMSG strain was higher than the simultaneously recorded OI strain 0.5+/-0.7% strain at the walk and 2.2+/-1.1% strain at the trot. Post-operative OI strains were only slightly higher than pre-operative values. Failure strains of in vivo instrumented SLs were 2.0+/-1.2% strain higher, and failure forces were slightly lower, than those of the contra lateral SLs that were instrumented post mortem. SL strains appeared to be considerably higher than those found in earlier acute experiments. Differences between in vivo LMSG and OI strains, supported by lower failure strains comparing in vivo and post mortem instrumented SLs, revealed that local changes in tendon mechanical properties occurred within 3 to 4 days after transducer implantation. Therefore, measurements of normal physiological tendon strains should be performed as soon as possible after transducer implantation.

Influence of shoeing on ground reaction forces and tendon strains in the forelimbs of ponies.

Strains in the superficial digital flexor tendon (SDFT), deep digital flexor tendon (DDFT), accessory ligament of the deep digital flexor muscle (inferior check ligament [ICL]) and the interosseus medius muscle (suspensory ligament [SL]) in the right forelimb of 5 ponies were measured using mercury-in-silastic strain gauges a few hours after implantation. Tendon strains were recorded at the walk with normal flat shoes, egg-bar shoes, a 7 degrees increased hoof angle accomplished by application of a heel-wedge and a 7 degrees decreased hoof angle using a toe-wedge, consecutively. Ground reaction forces were recorded with all 4 shoe types preoperatively and with flat shoes post operatively. The strain patterns of the SDFT, DDFT and SL showed a rapid increase at the beginning of the stance phase, followed by a plateau with a small incline or decline and a rapid decrease at the end of the stance phase. The SDFT had its maximal strain in the first half of the stance phase in all ponies. The DDFT and SL reached their maximal strain in the first half of the stance phase in 2 ponies and in the second half of the stance phase in the other 3 ponies. The ICL was strained maximally in the second half of the stance phase in all ponies. Averaged over all 5 ponies, the maximal strains in the SDFT, DDFT, ICL and SL with normal flat shoes were 2.4, 1.3, 5.4 and 3.7%, respectively. If an egg-bar was applied the mean peak strain in the DDFT was 0.13% lower and strain in the SL was 0.22% higher. With a heel-wedge, strain decreased in the DDFT and ICL (0.19% and 0.4%, respectively) and increased by 0.24% in the SL. A toe-wedge increased strain in the ICL by 0.8%. All changes mentioned were statistically significant (P < 0.1). The changes in tendon strain as a result of different types of shoeing correlated with changes in calculated torque's of the ground reaction force acting on the coffin joint.

Tendon strain in the forelimbs as a function of gait and ground characteristics and in vitro limb loading in ponies.

Strains in the tendons of the m. flexor digitalis superficialis (superficial digital flexor, SDFT) and m. flexor digitalis profundus (deep digital flexor, DDFT) tendons, the accessory ligament of the deep digital flexor muscle (inferior check ligament, ICL) and the m. interosseus medius (suspensory ligament, SL) of 5 ponies were recorded at the walk and trot using mercury-in-silastic strain gauges (MISS), on a hard surface (brick pavement) and on sand. The horses were shod with normal, flat shoes. On pavement, strain in the SDFT, DDFT and SL increased significantly from the walk (2.19%, 1.15% and 3.36%, respectively) to the trot (4.15%, 1.70% and 5.78%, respectively), but that in the ICL did not change significantly (5.36% at the walk, 4.88% at the trot). Strains in the ICL and SL were higher on pavement than on sand (P < 0.1) and strains in the SDFT and DDFT were not significantly different. Tendon strain in the SDFT and SL, but not in the ICL and DDFT, increased (P < 0.1) in a pony at the walk on pavement with a rider. Post mortem loading of the same instrumented limbs revealed that the metacarpophalangeal joint could be further extended when the elbow joint was extended. The in vitro tendon strain was different from that in vivo, implying that results from in vitro limb loading tests have only limited value for assessing tendon functioning in vivo.

In vivo tendon forces in the forelimb of ponies at the walk, validated by ground reaction force measurements.

The load distribution over tendinous structures in the equine forelimb was studied by computing forces from in vivo signals of implanted liquid-metal strain gauges in 5 ponies. For validation, these tendon forces were converted to joint moments, which were summed and compared to the calculated joint moments caused by the ground reaction force. Mean peak forces per kilogram body weight (n = 5) amounted to 5.2 N/kg for the superficial digital flexor tendon, 3.8 N/kg for the deep digital flexor tendon, 7.3 N/kg for the distal accessory (check) ligament and 8.4 N/kg for the third interosseous muscle (suspensory ligament). The maximal moment exerted by the tendons about the fetlock joint differed 11 +/- 7% (average +/- SD, n = 5) from the maximal ground reaction force moment, which difference amounted to 17 +/- 15% for the coffin joint moments. These differences appeared to result to a substantial extent from errors in the moment arms. Therefore, the computed tendon forces were considered to be sufficiently reliable.

Strain of the musculus interosseus medius and its rami extensorii in the horse, deduced from in vivo kinematics.

The in vivo strains of the musculus interosseus medius (suspensory ligament) and its rami extensorii (extensor branches) in the forelimb of the horse were determined from angular changes of the metacarpophalangeal and the distal interphalangeal joints. For this purpose, regression models were fitted to strains and joint angle combinations measured in in vitro limb loading experiments. The in vivo strains were computed from the kinematics of 8 horses at the walk, the trot and the canter. It was found that the extensor branches were strained about 1.0% at hoof impact, which indicates that they passively extend the interphalangeal joints just prior to impact and prevent flexion of the pastern joint just thereafter. The maximal strain of the suspensory ligament amounted to 3.4% at the walk, 5.6% at the trot and 6.3% at a slow canter.

Quantitative analysis of computer-averaged electromyographic profiles of intrinsic limb muscles in ponies at the walk.

The function of several intrinsic muscles of the fore-and hind limbs of 5 ponies walking normally was evaluated via surface electromyography. Electromyographic signals were band-pass filtered, rectified, linear enveloped, and standardized to the stride duration. Mean data from the muscles of the left and right limbs that were obtained from at least 30 strides in 2 recording sessions were recorded as electromyographic signals-time curves. The timing of muscle activity was determined from these graphs. On the basis of the major peaks in the electromyographic signal, muscle functions were identified. In the forelimb, the extensor carpi radialis muscle was involved in extension of the carpus at the end of the swing phase of the stride, and it provided support to flexion of the cubital joint at the beginning of the swing phase. The common digital extensor muscle extended the distal joints of the forelimb at the end of the swing phase. The ulnaris lateralis muscle provided support to extension of the cubital joint at the beginning of the stance phase, and the flexor carpi radialis muscle flexed the carpus at the beginning of the swing phase. The flexor carpi ulnaris muscle extended the cubital joint at the end of the swing phase. In the hind limb, the long digital extensor muscle flexed the tarsus at the beginning of the swing phase and extended the digital joints preceding the stance phase. The deep digital flexor muscle prevented overextension of the distal interphalangeal joint during the stance phase and flexion of the digital joints during the swing phase.(ABSTRACT TRUNCATED AT 250 WORDS)

A kinematic and strain gauge study of the reciprocal apparatus in the equine hind limb.

Hind limb kinematics were recorded in five horses at walk and trot using an opto-electronic CODA-3 system. Simultaneously, in vivo strain in the completely tendinous peroneus tertius muscle was registered by implanted mercury-in-silastic strain gauges. The origin-insertion length patterns of the peroneus tertius were calculated from raw kinematic data and from data corrected for the error caused by skin displacement, and compared with the directly measured strain. The strain patterns calculated from externally measured kinematic data appeared to be in accordance with the directly measured strain gauge data. However, a correction for skin displacement is an obligatory prerequisite to obtain reliable results. The amplitudes of strain did not exceed 3% and appeared to be of about the same magnitude at both walk and trot.