In silico evidence of superantigenic features in ORF8 protein from COVID-19

Very early on COVID-19 pandemic outbreak, it was noted that the some of the virus-induced clinical conditions resembled features of toxaemia caused by the toxic shock syndrome toxin type 1, which is a soluble superantigen produced by Staphylococcus aureus. Among all SARS proteins, the ORF8 protein from SARS-2 virus is significantly different from other known SARS-like coronaviruses, and therefore could exhibit unique pathogenic properties. We assess if ORF8 protein bears super antigenic features using in silico tools. We show that ORF8 has properties of an extracellular soluble protein and shares a significant degree of amino acid sequence identity with toxic shock syndrome toxin. Besides, docking and binding affinity analyses between monomeric and homodimeric ORF-8 with Vβ 2.1 and TRBV11-2 reveal strong interaction and high binding affinity. ORF8-TRBV11-2 strong interaction can contribute to the observed clonal expansion of that chain during COVID-19-associated multisystem inflammatory syndrome. Taken together, the evidence presented here supports the hypothesis that ORF8 protein from SARS-2 bears super antigenic properties.

A Fatal Case of Streptococcal Toxic Shock Syndrome Caused By Genotype Emm1 In The Third Trimester of Pregnancy, China

Background: Group A streptococcal (GAS) toxic shock syndrome (TSS) is a rare invasive disease, causing a high risk of maternal and fetal mortality during pregnancy. We report a fatal case of a female caused by GAS-TSS in the third trimester of pregnancy in Guangzhou, China. Case presentation: The patient is a 33-year-old female who presented at 37 weeks’ gestation with a history of three hours fever. The patient underwent an early onset and rapid progression with dramatic clinical picture and laboratory characters within 24 hours. The neonate survived after an aggressive anti-infection treatment.The GAS strains were isolated from two bottles of blood cultures and airway secretion culture, which confirmed as Streptococcus pyogenes associated with genotype emm1 by molecular analysis.Conclusion: Dramatic clinical picture and laboratory characters of the pregnant woman presented here might help improve clinicians' awareness and recognition of Streptococcus pyogenes, which could be of great importance for the early diagnosis of GAS- TSS in pregnancy.

Toxic shock syndrome complicated with symmetrical peripheral gangrene after liposuction and fat transfer: a case report and literature review

Background Liposuction is one of the most commonly performed aesthetic procedures. Toxic shock syndrome(TSS) is a rare, life-threatening complication. The incidence rate of TSS is very low in the plastic surgery field, especially after liposuction and fat transfer. Case presentation A 23-year-old female patient was transferred to our emergency department from an aesthetic clinic with sepsis shock features after received liposuction and fat transfer. The patient underwent TSS, disseminated intravascular coagulation(DIC), multiple organ dysfunction syndrome (MODS), symmetrical peripheral gangrene (SPG), and necrotizing soft tissue infection of the buttocks in the next 10 days. Authors used a series of debridement and reconstructive surgery including vacuum sealing drainage (VSD) treatment, artificial dermis grafts,split-thickness skin grafts, amputation surgeries when her vital signs were stable. The patient experienced desquamation of the hand on the 26th day. The skin grafts survived and the function of both fingers and toes recovered. She was discharged 2 months after admission and was in good health. Conclusion TSS is extremely rare in the field of liposuction and autologous fat transfer. The mortality rate of TSS is very high. Early diagnosis and operative treatment, as well as correction of systemic abnormalities, are the important keys to save a patient's life.

1370. Role of Clindamycin Versus Linezolid for Serious Group A Streptococcal Infections

Background Streptococcus pyogenes can cause severe illnesses such as toxic-shock syndrome and necrotizing fasciitis due to pyrogenic exotoxins. Clindamycin is added to penicillin for treatment of severe S. pyogenes infections as it is a bacterial protein synthesis inhibitor which reduces toxin production. However, clindamycin is associated with several adverse effects including C. difficile infection. Linezolid is a bacterial protein synthesis inhibitor that has been shown to provide excellent coverage of S. pyogenes including toxin inhibition in vitro, but clinical evidence is lacking. We compared outcomes of patients treated with linezolid versus clindamycin for serious S. pyogenes infections. Methods This was a retrospective study of patients with necrotizing fasciitis or toxic shock syndrome caused by S. pyogenes admitted to the Shock Trauma Center at University of Maryland Medical Center treated with at least 48 hours of either clindamycin or linezolid. Data collected included Sequential Organ Failure Assessment (SOFA) and Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) severity scores, time to resolution of infection, number of surgeries, C. difficile infection, other antibiotic associated adverse effects, and mortality. Associations between patient characteristics, antibiotic groups, and outcomes were analyzed using the chi-square test, Fisher’s exact test and t-test or Wilcoxon rank-sum test as appropriate (SAS v 9.4). Results 52 patients were included, 26 treated with clindamycin and 26 with linezolid. Most patients (85% clindamycin and 96.2% linezolid) were treated for necrotizing fasciitis. Baseline characteristics, including SOFA and LRINEC scores, were similar between the groups. There was no difference in mortality between patients treated with clindamycin versus linezolid (11.5% vs. 7.7%, p = 0.22), and resolution of infection was similar between the groups (92.3% vs. 88.5%, p = 1.0). There was no difference in adverse effects between the clindamycin and linezolid groups, including C. difficile infection (3.9% vs. 0% p = 1.0) and thrombocytopenia (30.8% vs. 42.3%, p = 0.4). Conclusion Linezolid could be an alternate to clindamycin for the treatment of serious toxin producing S. pyogenes infections. Further prospective studies are needed. Disclosures Emily Heil, PharmD, MS, BCIDP, Nothing to disclose

AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A Streptococcus

Streptococcus pyogenes (group A Streptococcus (GAS) is an important human pathogen that can cause severe invasive infection, such as necrotizing fasciitis and streptococcal toxic shock syndrome. The mortality rate of streptococcal toxic shock syndrome ranges from 20% to 50% in spite of antibiotics administration. AR-12, a pyrazole derivative, has been reported to inhibit the infection of viruses, intracellular bacteria, and fungi. In this report, we evaluated the bactericidal activities and mechanisms of AR-12 on GAS infection. Our in vitro results showed that AR-12 dose-dependently reduced the GAS growth, and 2.5 μg/mL of AR-12 significantly killed GAS within 2 h. AR-12 caused a remarkable reduction in nucleic acid and protein content of GAS. The expression of heat shock protein DnaK and streptococcal exotoxins was also inhibited by AR-12. Surveys of the GAS architecture by scanning electron microscopy revealed that AR-12-treated GAS displayed incomplete septa and micro-spherical structures protruding out of cell walls. Moreover, the combination of AR-12 and gentamicin had a synergistic antibacterial activity against GAS replication for both in vitro and in vivo infection. Taken together, these novel findings obtained in this study may provide a new therapeutic strategy for invasive GAS infection.