This prospective nonrandomized open-label cohort study addresses the safety and efficacy of exosomes (ExoFloÔ) derived from allogeneic bone marrow mesenchymal stem cells as treatment for severe COVID-19. During April 2020, ExoFlo was provided to 24 SARS-CoV-2 polymerase chain reaction-positive patients at a single hospital center, all of whom met criteria for severe COVID-19 as well as moderate-to-severe acute respiratory distress syndrome. Patients received a single 15 mL intravenous dose of ExoFlo and were evaluated for both safety and efficacy from days 1 to 14 post-treatment. All safety endpoints were met with no adverse events observed within 72 h of ExoFlo administration. A survival rate of 83% was observed. In total, 17 of 24 (71%) patients recovered, 3 of 24 (13%) patients remained critically ill though stable, and 4 of 24 (16%) patients expired for reasons unrelated to the treatment. Overall, after one treatment, patients' clinical status and oxygenation improved with an average pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO 2 / FiO 2 ) increase of 192% (P < 0.001). Laboratory values revealed significant improvements in absolute neutrophil count [mean reduction 32% (P value <0.001)] and lymphopenia with average CD3 + , CD4 + , and CD8 + lymphocyte counts increasing by 46% (P < 0.05), 45% (P < 0.05), and 46% (P < 0.001), respectively. Likewise, acute phase reactants declined, with mean C-reactive protein, ferritin, and D-dimer reduction of 77% (P < 0.001), 43% (P < 0.001), and 42% (P < 0.05), respectively. In conclusion, owing to its safety profile, capacity to restore oxygenation, downregulate cytokine storm, and reconstitute immunity, ExoFlo is a promising therapeutic candidate for severe COVID-19. Future randomized controlled trials (RCTs) are needed to determine ExoFlo therapeutic potential.

Two classes of rotating neutron stars-soft gamma-ray repeaters (SGRs) and anomalous X-ray pulsars-are magnetars, whose X-ray emission is powered by a very strong magnetic field (B approximately 10(15) G). SGRs occasionally become 'active', producing many short X-ray bursts. Extremely rarely, an SGR emits a giant flare with a total energy about a thousand times higher than in a typical burst. Here we report that SGR 1806-20 emitted a giant flare on 27 December 2004. The total (isotropic) flare energy is 2 x 10(46) erg, which is about a hundred times higher than the other two previously observed giant flares. The energy release probably occurred during a catastrophic reconfiguration of the neutron star's magnetic field. If the event had occurred at a larger distance, but within 40 megaparsecs, it would have resembled a short, hard gamma-ray burst, suggesting that flares from extragalactic SGRs may form a subclass of such bursts.

The soft-gamma repeater SGR 1900 + 14 became active again on June 1998 after a long period of quiescence; it remained at a low state of activity until August 1998, when it emitted a series of extraordinarily intense outbursts. We have observed the source with RXTE twice, during the onset of each active episode. We confirm the pulsations at the 5.16 s period reported earlier (Hurley et al. 1998b) from SGR 1900 + 14 . Here we report the detection of a secular spindown of the pulse period at an average rate of 1.1 × 10 −10 s/s. In view of the strong similarities between SGRs, we attribute the spindown of SGR 1900 + 14 to magnetic dipole radiation, possibly accelerated by a quiescent flux, as in the case of SGR 1806 − 20 (Kouveliotou et al. 1998a).This allows an estimate of the pulsar dipolar magnetic field, which is 2 − 8 × 10 14 G. Our results confirm that SGRs are magnetars.

An outburst of more than 80 individual bursts, similar to those seen from Soft Gamma Repeaters (SGRs), was detected from the anomalous X-ray pulsar (AXP) 1E 2259+586 in 2002 June. Coincident with this burst activity were gross changes in the pulsed flux, persistent flux, energy spectrum, pulse profile, and spin-down of the underlying X-ray source. We present Rossi X-Ray Timing Explorer and X-Ray Multi-Mirror Mission observations of 1E 2259+586 that show the evolution of the aforementioned source parameters during and following this episode and identify recovery timescales for each. Specifically, we observe an X-ray flux increase (pulsed and phase-averaged) by more than an order of magnitude having two distinct components. The first component is linked to the burst activity and decays within $2 days, during which the energy spectrum is considerably harder than during the quiescent state of the source. The second component decays over the year following the glitch according to a power law in time with an exponent À0:22 AE 0:01. The pulsed fraction decreased initially to $15% rms but recovered rapidly to the preoutburst level of $23% within the first 3 days. The pulse profile changed significantly during the outburst and recovered almost fully within 2 months of the outburst. A glitch of size Á max = ¼ (4:24 AE 0:11) ; 10 À6 was observed in 1E 2259+586, which preceded the observed burst activity. The glitch could not be well fitted with a simple partial exponential recovery. An exponential rise of $20% of the frequency jump with a timescale of $14 days results in a significantly better fit to the data; however, contamination from a systematic drift in the phase of the pulse profile cannot be excluded. A fraction of the glitch ($19%) was recovered in a quasi-exponential manner having a recovery timescale of $16 days. The long-term postglitch spin-down rate decreased in magnitude relative to the preglitch value. The changes in the source properties of 1E 2259+586 during its 2002 outburst are shown to be qualitatively similar to changes seen during or following burst activity in two SGRs, thus further solidifying the common nature of SGRs and AXPs as magnetars. The changes in persistent emission properties of 1E 2259+586 suggest that the star underwent a plastic deformation of the crust that simultaneously impacted the superfluid interior (crustal and possibly core superfluid) and the magnetosphere. Finally, the changes in persistent emission properties coincident with burst activity in 1E 2259+586 enabled us to infer previous burst-active episodes from this and other AXPs. The nondetection of these outbursts by all-sky gamma-ray instruments suggests that the number of active magnetar candidates in our Galaxy is larger than previously thought.