COVID-19 Convalescent Plasma Therapy Decreases Inflammatory Cytokines: A Randomized Controlled Trial

This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity

Dynamics of Inflammatory Responses After SARS-CoV-2 Infection by Vaccination Status in the USA: A Prospective Cohort Study

BACKGROUND: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection. METHODS: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples and symptom data collected at screening (pre-transfusion), day 14, and day 90 visits. Associations between COVID-19 vaccination status and concentrations of 21 cytokines and chemokines (measured using multiplexed sandwich immunoassays) were examined using multivariate linear mixed-effects regression models, adjusted for age, sex, BMI, hypertension, diabetes, trial group, and COVID-19 waves (pre-alpha or alpha and delta). FINDINGS: Between June 29, 2020, and Sept 30, 2021, 882 participants recently infected with SARS-CoV-2 were enrolled, of whom 506 (57%) were female and 376 (43%) were male. 688 (78%) of 882 participants were unvaccinated, 55 (6%) were partly vaccinated, and 139 (16%) were fully vaccinated at baseline. After adjusting for confounders, geometric mean concentrations of interleukin (IL)-2RA, IL-7, IL-8, IL-15, IL-29 (interferon-λ), inducible protein-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α were significantly lower among the fully vaccinated group than in the unvaccinated group at screening. On day 90, fully vaccinated participants had approximately 20% lower geometric mean concentrations of IL-7, IL-8, and vascular endothelial growth factor-A than unvaccinated participants. Cytokine and chemokine concentrations decreased over time in the fully and partly vaccinated groups and unvaccinated group. Log INTERPRETATION: Initially and during recovery from symptomatic COVID-19, fully vaccinated participants had lower concentrations of inflammatory markers than unvaccinated participants suggesting vaccination is associated with short-term and long-term reduction in inflammation, which could in part explain the reduced disease severity and mortality in vaccinated individuals. FUNDING: US Department of Defense, National Institutes of Health, Bloomberg Philanthropies, State of Maryland, Mental Wellness Foundation, Moriah Fund, Octapharma, HealthNetwork Foundation, and the Shear Family Foundation

Gomphos shevyrevae Meng & Kraatz & Wang & Ni & Gebo & Beard 2009, new species

Gomphos shevyrevae, new species HOLOTYPE: A right M1 (IVPP V 14669). PARATYPE: A right m1 (IVPP V 14670). INCLUDED SPECIMENS: A right P4 (or P3) (V14671.1), a right M1 (V14671.2), a right M2 (V14671.3), a left M2 (V14671.4), a right m1 (V14672.1), a right m2 (V14672.2), a left m3 (V14672.3), a left calcaneus (V14673), and a left astragalus (V14674). ETYMOLOGY: The species name is in honor of N.S. Shevyreva who named Gomphos elkema. DIAGNOSIS: Differs from Gomphos elkema and G. ellae in having more robust teeth with higher crowns, inflated cusps; upper molars with more posteriorly expanded hypocone and shelf; absence of the ridge connecting the lingual and labial cusps on P4; lower molars with relatively long trigonid and short talonid, reduced mesoconid and hypoconulid, and absence of the mesostylid; further differs from G. elkema in having extra facets on the calcaneus for articulation with the astragalus and navicular (unknown for G. ellae). TYPE LOCALITY AND AGE: Huheboerhe escarpment, Erlian Basin of Nei-Mongol, Middle Eocene lower beds of the Irdin Manha Formation. COMPARATIVE DESCRIPTION: Measurements of all teeth are in table 1. The tooth we identified as a P4 could also be a P3 (fig. 2). However, the anterior border of P3 is usually narrower than the posterior border in Gomphos. This tooth has its anterior portion TABLE 1 Tooth measurements of Gomphos shevyrevae (in mm) as wide as the posterior and bears a tiny posterolingual cusp, suggesting that it is likely a right P4. The P4 is a recently erupted tooth that bears no wear. As is typical of Gomphos, the P4 is unilaterally hypsodont and consists of a lingual main cusp, presumably the protocone, and a labial cusp. The lingual cusp is crescent shaped, and its two lophs form the anterior and posterior edges of the tooth. The labial cusp is conical, having a steeper labial surface and a more rounded lingual surface. Unlike P4 of Gomphos elkema, in which P4 is known (Meng et al., 2004; Asher et al., 2005), the ridge connecting the two cusps is absent in G. shevyrevae; instead, there is a weak ridge extending from the labial cusp anterolingually to join the midpoint of the anterior loph. The absence of a connection between the lingual and labial cusps of P4 recalls the condition found in Mimotona (Li, 1977; Li and Ting, 1993). Upper molars have one major lingual and two minor labial roots. The enamel is thick. M1 is so assigned because its hypocone and shelf are less expanded posteriorly than those of M2, and M1 is usually proportionally shorter than M2 (fig. 2). M1 of G. shevyrevae is similar to that of G. elkema in general morphology. However, the M1 and other upper cheek teeth of G. shevyrevae are more robust with more inflated cusps and stronger lophs. The protocone and its anterior and posterior lophs form a V-shaped structure with a slightly rounded apex (the lingual side of the protocone). The angle created by the lophs is about 45 °. The lingual portion of the anterior loph may be homologized with the preprotocrista and the labial portion, which is much thinner, with the preparaconule crista. A paraconule (protoconule) is not distinct, but is indicated by a slight inflation where the postparaconule crista joins the anterior loph. Absence of the paraconule is common in basal Glires, both in simplicidentates, such as Matutinia and Rhombomylus (Ting et al., 2002; Meng et al., 2003), and duplicidentates, such as Mimotona and Gomphos (Li, 1977; Li and Ting, 1993; Meng et al., 2004), but it is usually present in taxa that are more closely related to rodents and in basal rodents, such as Tribosphenomys (Meng et al., 1994, 2007b; Meng and Wyss, 2001), Neimengomys (Meng et al., 2007b), Archetypomys (Meng et al., 2007a), and Cocomys (Li et al., 1989). There is a weak ridge between the paracone and the anterior loph, which is probably the postparaconule crista. The metacone is small- er and more lingually positioned than the paracone. It is connected with the protocone by the posterior loph of the protocone. The latter loph is strong, almost as wide as the metacone. A mesostyle occurs at the posterior base of the paracone, which blocks the labial exit of the narrow trigon basin. The metaconule is present, but is difficult to distinguish in heavily worn specimens. In lightly worn specimens (fig. 2E) a broader wear facet indicates the metaconule that must be higher and broader than the crista in order for such a wear pattern to be created. In G. elkema the posterior loph of the protocone is relatively slimmer and there is usually a restriction labial to the protocone. The hypocone and the postcingulum are well developed, and both structures are expanded posteriorly. The hypocone is separated from the protocone by a transverse groove, and a similar condition occurs on M2. This condition appears to differ from the morphology prevailing in G. elkema and G. ellae. In well-worn specimens (fig. 2C), however, the protocone and hypocone become confluent. On the lingual surface of the tooth, a vertical groove between the protocone and hypocone exists near the occlusal surface of the tooth, and this feature also seems more pronounced than on upper molars of G. elkema and G. ellae. M2 is similar to M 1 in general morphology, but it is proportionally longer. The mesostyle is reduced, either being incorporated into the posterior base of the paracone or entirely absent. No M3 was collected. The lower molars have an anterior and a posterior root. The tooth crown is somewhat higher than that of G. elkema and G. ellae. As in the upper molars, the enamel appears thicker than that of G. elkema and G. ellae. The m1 is identified as such because it has a transversely oriented, ridgelike hypoconulid (fig 3). In Gomphos, the lower molar hypoconulid becomes more pronounced posteriorly. The m1 and m2 are very similar except that m2 has a more posteriorly projecting hypoconulid. The lower molars are proportionally wider, and therefore relatively shorter, than those of other species of the genus. Lower molar trigonids are proportionally longer in relation to their corresponding talonid than is the case in other species of the genus. As is typical of Gomphos, the protoconid and metaconid are transversely aligned, and the trigonid has nearly vertical anterior and posterior walls. The protoconid and the metaconid are subequal in size. The protoconid is worn more extensively and is therefore lower than the metaconid. The protoconid sends the paralophid (paracristid) to the anterolingual base of the metaconid and the protolophid (protocristid) to the posterior base of the metaconid. A crescentic trigonid basin is enclosed by the trigonid cusps and lophids. Lower molar talonids are as wide as the trigonid and are longer than their corresponding trigonid. The hypoconid is as large as the protoconid and is very close to the posterior wall of the trigonid, so that the hypoflexid becomes a narrow groove. The cristid obliqua (ectolophid) is short and the mesoconid appears very weak relative to other mimotonids. The entoconid is low. Unlike the condition in G. elkema and G. ellae, in which a mesostylid is present (Meng et al., 2004; Kraatz et al., 2009), the mesostylid is absent in the new species. Because of the reduction of the mesoconid and cristid obliqua, the talonid basin is a broad, featureless concavity. The hypoconulid is a transverse ridge at the rear of the tooth, being connected with the entoconid by a strong postcristid. The m3 is little worn and displays several additional minor cuspules on the occlusal surface; these structures would be quickly removed with wear (fig. 3). The m3 differs from m1 and m 2 in having a longer talonid and a more pronounced hypoconulid. However, compared to those of G. elkema and G. ellae, the talonid of G. shevyrevae is relatively shorter and the hypoconulid is reduced; it does not form a projection at the posterior end of the tooth. The astragalus measures 11.34 mm long and 8.82 mm wide (maximum dimensions) and is partly broken at its head (fig. 4A). The morphology of the preserved portion is identical to that of Gomphos elkema (Meng et al., 2004). The bone is ventrodorsally (or anteroposteriorly) flat. The trochlea is transversely broad and shallow. In G. elkema, the lateral and medial rims of the astragalar trochlea appear to be more asymmetrical, with the lateral much larger than the medial (Meng et al., 2004). The calcaneus measures 20.8 mm long and 8.93 mm wide (maximum dimensions; fig. 4B). It is typical of Gomphos in that the calcaneoastragalar and sustentacular facets are aligned at the same level, similar to that of lagomorphs (Bleefeld and McKenna, 1985), but the bone lacks a calcaneal canal that is characteristic of lagomorphs (Bleefeld and Bock, 2002). The calcaneoastragalar facet is a narrow, long and convex surface in a proximodistal orientation, nearly parallel to the long axis of the bone, whereas the sustentacular facet is rounded and concave. Although the general morphology of the calcaneus is similar to that of G. elkema, it differs from the latter in having a facet on the distal side of the bone, which probably articulates with the navicular and astragalus. This feature does not occur in known astragali of G. elkema (Meng et al., 2004, 2005; Asher et al., 2005), and is most likely a derived feature of G. shevyrevae. However, in Mimolagus, a similar facet is present on the calcaneus, which is in articulation with the astragalus (Bohlin, 1951).Published as part of Meng, Jin, Kraatz, Brian P., Wang, Yuanqing, Ni, Xijun, Gebo, Daniel L & Beard, K. Christopher, 2009, A New Species of Gomphos (Glires, Mammalia) from the Eocene of the Erlian Basin, Nei Mongol, China, pp. 1-12 in American Museum Novitates 3670 on pages 4-7, DOI: 10.1206/673.1, http://zenodo.org/record/471299

Neimengomys MENG & NI & LI & BEARD & GEBO & WANG & WANG 2007, new genus

<i>Neimengomys</i>, new genus <p> TYPE SPECIES: <i>Neimengomys qii</i>, new species</p> <p> ETYMOLOGY: <i>Nei-Meng</i> is Chinese (in pinyin) for ‘‘Inner Mongolia’’; <i>mys</i> is Greek for ‘‘mouse’’, in analogy with <i>Alagomys</i> and <i>Tribosphenomys.</i></p> <p> DIAGNOSIS: Differs from <i>Alagomys</i> but resembles <i>Tribosphenomys</i> in having a buccal shelf and a hypocone on upper molars, a more transverse M3 with conical cusps, and a narrower talonid basin. Differs from <i>Tribosphenomys</i> in having a P4 with a weak buccal shelf, a more inflated protocone on upper molars, a more inflated and buccally positioned hypocone, and a smaller hypoconulid on lower molars.</p>Published as part of <i>MENG, JIN, NI, XIJUN, LI, CHUANKUI, BEARD, K. CHRISTOPHER, GEBO, DANIEL L., WANG, YUANQING & WANG, HONGJIANG, 2007, New Material Of Alagomyidae (Mammalia, Glires) From The Late Paleocene Subeng Locality, Inner Mongolia, pp. 1-32 in American Museum Novitates 3597 (1)</i> on page 15, DOI: 10.1206/0003-0082(2007)3597[1:NMOAMG]2.0.CO;2, <a href="http://zenodo.org/record/4735366">http://zenodo.org/record/4735366</a&gt

Neimengomys qii MENG & NI & LI & BEARD & GEBO & WANG & WANG 2007

Neimengomys qii, new spesies HOLOTYPE: IVPP V14711.1, a right M1 (or M2) (fig. 13b). INCLUDED SPECIMENS: V 14711.2, left P4; V 14711.3–10, 8 M1s and/or M2s; V 14711.11–14, 4 M3S (or M2s); V 14712.1, right p4; V 14712.2, right m1; V 14712.3–5, 14712.3–5, 3 m3s (fig. 13). See table 5 for measurements. ETYMOLOGY: The trivial name is after Qi Tao (IVPP), who made the first discovery of Tribosphenomys specimens by screenwashing at Subeng in the 1980s. DIAGNOSIS: Same as for the genus. TYPE LOCALITY AND AGE: Subeng, about 25 km west of Erlian, Gashatan, Late Paleocene. COMPARATIVE DESCRIPTION: A P4 is identified for this species (fig. 13a). This tooth is smaller than those of T. minutus and transversely oval-shaped. The P4 buccal shelf is much narrower than that of T. minutus and is similar to that of A. inopinatus (Dashzeveg, 1990b). It differs from both Tribosphenomys and Alagomys in bearing a very small cuspule on the buccal shelf. Nine upper cheek teeth are considered to be either M1 or M2 (fig. 13b–j), which we cannot yet distinguish with confidence. These teeth have an oval shape in occlusal view. Compared to M1 of Tribosphenomys minutus these teeth are narrower and less symmetrical along the transverse axis, the protocone is more inflated, the hypocone is more inflated and buccally positioned, and the buccal shelf of the tooth is distinctly narrower. The width/ length ratio of these teeth is similar to that of M2 of T. minutus, but M2 of T. minutus is more triangular in occlusal view, the anterior edge of the tooth is much wider than its posterior counterpart, the protocone is anteroposteriorly more compressed, and the hypocone is usually absent. These teeth are also distinctive in size and morphology from upper molars of T. secundus (Lopatin and Averianov, 2004a). The molars of Neimengomys qii differ from M1 and/or M2 of Alagomys in having a hypocone and a more prominent buccal shelf. Among species of Alagomys, N. qii is more comparable with the North American A. russelli than the Asian A. inopinatus and A. oriensis. The Asian species are similar in have an anteroposteriorly compressed protocone, while A. russelli has an inflated protocone and a somewhat oval-shaped occlusal outline (Dawson and Beard, 1996: plate 1F). Subeng specimens differ from A. russelli in having a distinct buccal shelf on the upper molars, whereas the same structure is completely absent in A. russelli. In addition, the molar cusps of A. russelli are less isolated, the lophs are stronger, the protocone is more inflated, and the trigon basin is deeper. In addition, the basin and postcingulum between the protocone and metaconule are more prominent in Subeng specimens. Four specimens are identified as M3s (fig. 13k–n) of Neimengomys qii because of their small size and reduced metacone. Compared to M3 of T. minutus, the M3 of N. qii is also oval-shaped and has a more inflated, conical protocone. The M3 of N. qii is more transverse and cuspate than those of Alagomys (Dawson and Beard, 1996; Tong and Dawson, 1995). However, we cannot rule out the possibility that these teeth are M2. One p4 is identified as N. qii because of its smaller size and unique morphology. Unlike those referred to T. minutus, the p4 (fig. 13o) has a narrow trigonid consisting of two closely appressed cusps. In contrast, the talonid is wider than the trigonid and formed by two transverse, ridgelike cuspids. The p4 is similar in morphology to that of T. secundus (Lopatin and Averianov, 2004a), but differs in being much smaller. The m1 of N. qii (fig. 13p) has a narrower trigonid than those of T. minutus and a hypoconulid that is aligned with the entoconid as a ridge. Three m3s are referred to T. qii (fig. 13q–s). The hypoconulid on these m3s is more transverse than conical, differing from those referred to T. minutus. The trigonid basin of the lower molar is somewhat restricted, similar to that of T. minutus. In contrast, the trigonid basin in Alagomys is more open. Although the material is fragmentary, the morphologies of these teeth show that they must be from a previously unknown taxon. Based on these specimens, we propose a new genus and species of alagomyid.Published as part of MENG, JIN, NI, XIJUN, LI, CHUANKUI, BEARD, K. CHRISTOPHER, GEBO, DANIEL L., WANG, YUANQING & WANG, HONGJIANG, 2007, New Material Of Alagomyidae (Mammalia, Glires) From The Late Paleocene Subeng Locality, Inner Mongolia, pp. 1-32 in American Museum Novitates 3597 (1) on pages 16-21, DOI: 10.1206/0003-0082(2007)3597[1:NMOAMG]2.0.CO;2, http://zenodo.org/record/473536