Respiratory failure in the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is hypothesized to be driven by an overreacting innate immune response, where the complement system is a key player. In this prospective cohort study of 39 hospitalized coronavirus disease COVID-19 patients, we describe systemic complement activation and its association with development of respiratory failure. Clinical data and biological samples were obtained at admission, days 3 to 5, and days 7 to 10. Respiratory failure was defined as PO2/FiO2 ratio of ≤40 kPa. Complement activation products covering the classical/lectin (C4d), alternative (C3bBbP) and common pathway (C3bc, C5a, and sC5b-9), the lectin pathway recognition molecule MBL, and antibody serology were analyzed by enzyme-immunoassays; viral load by PCR. Controls comprised healthy blood donors. Consistently increased systemic complement activation was observed in the majority of COVID-19 patients during hospital stay. At admission, sC5b-9 and C4d were significantly higher in patients with than without respiratory failure (P = 0.008 and P = 0.034). Logistic regression showed increasing odds of respiratory failure with sC5b-9 (odds ratio 31.9, 95% CI 1.4 to 746, P = 0.03) and need for oxygen therapy with C4d (11.7, 1.1 to 130, P = 0.045). Admission sC5b-9 and C4d correlated significantly to ferritin (r = 0.64, P < 0.001; r = 0.69, P < 0.001). C4d, sC5b-9, and C5a correlated with antiviral antibodies, but not with viral load. Systemic complement activation is associated with respiratory failure in COVID-19 patients and provides a rationale for investigating complement inhibitors in future clinical trials.

ObjectivesFacial lipoatrophy can be devastating for HIV-infected patients, with negative effects on self-esteem. In this study, we treated facial fat atrophy in the nasogenian area with hyaluronic acid (Restylane SubQ; Q-Med AB, Uppsala, Sweden). MethodsTwenty patients were included in the study. Treatment effects were evaluated at baseline, and at weeks 6, 24 and 52 using ultrasound, the Global Aesthetic Improvement Scale, the Visual Analogue Scale and the Rosenberg Self-Esteem Scale. ResultsMean (AE standard deviation) total cutaneous thickness increased from 6 AE 1 mm at baseline to 15 AE 3 mm at week 6 (Po0.001), and declined to 10 AE 2 mm at week 52 (Po0.001 vs baseline). The response rate (total cutaneous thickness 410 mm) was 100% at week 6, 85% at week 24 and 60% at week 52. At week 6, all of the patients classified their facial appearance as very much improved or moderately improved. They also reported increased satisfaction with their facial appearance and had higher self-esteem scores. At week 52, 15 of 19 patients still classified their facial appearance as very much improved or moderately improved, although the mean total cutaneous thickness had gradually declined. ConclusionsOur results indicate that Restylane SubQ is a useful and well-tolerated dermal filler for treating HIV-positive patients with facial lipoatrophy.

In SARS-CoV-2 infection there is an urgent need to identify patients that will progress to severe COVID-19 and may benefit from targeted treatment. In this study we analyzed plasma cytokines in COVID-19 patients and investigated their association with respiratory failure (RF) and treatment in Intensive Care Unit (ICU). Hospitalized patients (n = 34) with confirmed COVID-19 were recruited into a prospective cohort study. Clinical data and blood samples were collected at inclusion and after 2–5 and 7–10 days. RF was defined as PaO2/FiO2 ratio (P/F) < 40 kPa. Plasma cytokines were analyzed by a Human Cytokine 27-plex assay. COVID-19 patients with RF and/or treated in ICU showed overall increased systemic cytokine levels. Plasma IL-6, IL-8, G-CSF, MCP-1, MIP-1α levels were negatively correlated with P/F, whereas combinations of IL-6, IP-10, IL-1ra and MCP-1 showed the best association with RF in ROC analysis (AUC 0.79–0.80, p < 0.05). During hospitalization the decline was most significant for IP-10 (p < 0.001). Elevated levels of pro-inflammatory cytokines were present in patients with severe COVID-19. IL-6 and MCP-1 were inversely correlated with P/F with the largest AUC in ROC analyses and should be further explored as biomarkers to identify patients at risk for severe RF and as targets for improved treatment strategies.

ObjectivesFacial lipoatrophy can be a stigmatizing side effect of antiretroviral (AVR) treatment for HIV-infected patients. We sought to evaluate the long-term efficacy and safety of a new formulation of hyaluronic acid that can be injected in larger amounts and into deeper skin layers during 3 years of follow-up. Methods Twenty patients received injections of Restylane SubQ 2. Refill treatment was offered at 12 and 24 months. Treatment effects were evaluated using ultrasound, the Global Aesthetic Improvement Scale, visual analogue scale (VAS) and the Rosenberg self-esteem scale. ResultsSeventeen patients remained at 36 months. Mean (AE standard deviation) total cutaneous thickness increased from 6 AE 1 mm at baseline to 12 AE 1 mm (Po0.001) at 36 months. Response rate (total cutaneous thickness 410 mm) was 70%. Fifteen patients classified their facial appearance as very much or moderately improved. VAS increased from 39 AE 25 to 70 AE 20 (Po0.05) and higher self-esteem scores were reported. Local swelling and tenderness after treatment was common. Persistent papules found in several patients after treatment were removed effectively with hyaluronidase injections. Three patients, treated only at baseline, still had higher total cutaneous thickness scores at 36 months. ConclusionsOur results indicate that a large particle hyaluronic acid formulation is a durable and well-tolerated dermal filler for treating HIV-positive patients with facial lipoatrophy. IntroductionLipoatrophy is a particularly distressing aspect of lipodystrophy evident in HIV-positive patients on antiretroviral therapy (ART). Facial lipoatrophy can severely affect patients' quality of life and may contribute to reduced antiretroviral (AVR) adherence [1]. Furthermore, the stigmatization affected patients may encounter as a result of facial lipoatrophy can be detrimental for self-esteem [2]. Treatment strategies include switching AVR regimens, prescription of medication, insertion of surgical implants and injection of dermal fillers.While there is evidence that the use of new nonthymidine nucleoside reverse transcriptase inhibitors can prevent the development of lipoatrophy, switching medications, after lipoatrophy has progressed, offers only limited benefit [3,4]. A follow-up study of the Oslo HIV Cohort Study 2000 found that facial atrophy was less reversible than fat atrophy of the extremities [5]. Medications such as pioglitazone [6], uridine [7] and pravastatin [8] have been shown to have some effect on limb lipoatrophy in HIV-infected patients; however, the mechanisms by which they work and their potential side effects are not well documented.In the absence of a therapeutic intervention to reverse lipoatrophy, injection of soft-tissue fillers appears to be the simplest way to correct facial lipoatrophy. Many soft-tissue fillers, both biodegradable and permanent, have been studied in HIV facial lipoatrophy, however, long-term clinical safety and efficacy data are lacking. Biodegradable fillers have a good safety profile, but treatment with s...

Background: The pathogenesis of coronavirus disease 2019 (COVID-19) is still incompletely understood, but it seems to involve immune activation and immune dysregulation. Objective: We examined the parameters of activation of different leukocyte subsets in COVID-19-infected patients in relation to disease severity. Methods: We analyzed plasma levels of myeloperoxidase (a marker of neutrophil activation), soluble (s) CD25 (sCD25) and soluble T-cell immunoglobulin mucin domain-3 (sTIM-3) (markers of T-cell activation and exhaustion), and sCD14 and sCD163 (markers of monocyte/macrophage activation) in 39 COVID-19-infected patients at hospital admission and 2 additional times during the first 10 days in relation to their need for intensive care unit (ICU) treatment. Results: Our major findings were as follows: (1) severe clinical outcome (ICU treatment) was associated with high plasma levels of sTIM-3 and myeloperoxidase, suggesting activated and potentially exhausted T cells and activated neutrophils, respectively; (2) in contrast, sCD14 and sCD163 showed no association with need for ICU treatment; and (3) levels of sCD25, sTIM-3, and myeloperoxidase were inversely correlated with degree of respiratory failure, as assessed by the ratio of PaO 2 to fraction of inspired oxygen, and were positively correlated with the cardiac marker N-terminal pro-B-type natriuretic peptide. Conclusion: Our findings suggest that neutrophil activation and, in particular, activated T cells may play an important role in the pathogenesis of COVID-19 infection, suggesting that T-celltargeted treatment options and downregulation of neutrophil activation could be of importance in this disorder. (J Allergy Clin Immunol 2021;147:92-8.)