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Background Since December 2019, Coronavirus Disease 2019 (COVID-19) has become a global pandemic, causing mass morbidity and mortality. Prior studies in other respiratory infections suggest that convalescent plasma transfusion may offer benefit to some patients. Here, the outcomes of thirty-nine hospitalized patients with severe to life-threatening COVID-19 who received convalescent plasma transfusion were compared against a cohort of retrospectively matched controls. Methods Plasma recipients were selected based on supplemental oxygen needs at the time of enrollment and the time elapsed since the onset of symptoms. Recipients were transfused with convalescent plasma from donors with a SARS-CoV-2 (severe acute respiratory disease coronavirus 2) anti-spike antibody titer of ³1:320 dilution. Matched control patients were retrospectively identified within the electronic health record database. Supplemental oxygen requirements and survival were compared between plasma recipients and controls. Results Convalescent plasma recipients were more likely than control patients to remain the same or have improvements in their supplemental oxygen requirements by post-transfusion day 14, with an odds ratio of 0.86 (95% CI: 0.75∼0.98; p = 0.028). Plasma recipients also demonstrated improved survival, compared to control patients (log-rank test: p = 0.039). In a covariates-adjusted Cox model, convalescent plasma transfusion improved survival for non-intubated patients (hazard ratio 0.19 (95% CI: 0.05 ∼0.72); p = 0.015), but not for intubated patients (1.24 (0.33∼4.67); p = 0.752). Conclusions Convalescent plasma transfusion is a potentially efficacious treatment option for patients hospitalized with COVID-19; however, these data suggest that non-intubated patients may benefit more than those requiring mechanical ventilation.

This study sought to determine whether deficient Igf1 expression in osteocytes would affect loading-induced osteogenic response. Tibias of osteocyte Igf1 conditional knockout (KO) mice (generated by cross-breeding Igf1 floxed mice with Dmp1- Cre transgenic mice) and wild-type (WT) littermates were subjected to four-point bending for 2 wk. Microcomputed tomography confirmed that the size of tibias of conditional mutants was smaller. Loading with an equivalent loading strain increased periosteal woven bone and endosteal lamellar bone formation in WT mice but not in conditional KO mice. Consistent with the lack of an osteogenic response, the loading failed to upregulate expression of early mechanoresponsive genes ( Igf1, Cox-2, c-fos) or osteogenic genes ( Cbfa-1, and osteocalcin) in conditional KO bones. The lack of osteogenic response was not due to reduced osteocyte density or insufficient loading strain. Deficient osteocyte Igf1 expression reduced the loading-induced upregulation of expression of canonical Wnt signaling genes ( Wnt10b, Lrp5, Dkk1, sFrp2). The loading also reduced (by 40%) Sost expression in WT mice, but the loading not only did not reduce but upregulated (∼1.5-fold) Sost expression in conditional KO mice. Conditional disruption of Igf1 in osteocytes also abolished the loading-induced increase in the bone β-catenin protein level. These findings suggest an impaired response in the loading-induced upregulation of the Wnt signaling in conditional KO mice. In summary, conditional disruption of Igf1 in osteocytes abolished the loading-induced activation of the Wnt signaling and the corresponding osteogenic response. In conclusion, osteocyte-derived IGF-I plays a key determining role in bone mechanosensitivity.