Complete response to eculizumab in atypical hemolytic uremic syndrome with homozygous C3 mutation

Case Report: Atypical Hemolytic Uremic Syndrome (atypical HUS) is a rare and severe form of thrombotic microangiopathy (TMA) characterized by thrombocytopenia, intravascular hemolysis, and acute kidney injury with an incidence of 1 per million.1 Dysregulation and overactivation of the complement alternative pathway due to genetic mutations have been detected in 40-60% of patients with sporadic or familial atypical HUS.2,4 Triggers include viral illness, pregnancy, malignancy, sepsis, or sporadically with no known inciting event.1 Atypical HUS is a severe disease with a 2-10% risk of mortality, 33% risk of end-stage renal failure, and 50% chance of relapse.5 A 24-year-old female with prior history of atypical HUS at the age of 16 (with response to plasmapheresis) presented to the ER with a 5-day history of fever, chills, sore throat, nausea, vomiting, and dark urine. She tested positive for COVID-19. The exam revealed scleral icterus and scattered petechiae. Labs demonstrated nadir hemoglobin (Hgb) of 9.2 g/dL, platelet count of 52 000k/uL, haptoglobin < 30 mg/dL, peak LDH 1128U/L and creatinine 4.62 mg/dL. Urinalysis is consistent with hemoglobinuria. Schistocytes were noted on the peripheral smear. Rapid streptococcal antigen test and C3, C4, and IgA levels were unremarkable. Chest X-Ray, X-ray KUB, and ultrasound abdomen were unremarkable. The pregnancy test was negative. ADAMTS13 was >100%. Genetic analysis after the initial episode at age 16 revealed autosomal recessive inheritance c.193A > c gene mutations in C3. The patient received IV fluids, ceftriaxone for cystitis, and two units of Fresh Frozen Plasma. She initiated treatment with eculizumab. She also received the MENVEO and meningitis B vaccine per protocol due to the risk of meningitis from terminal complement deficiencies. After 4 infusions of eculizumab, patient's labs improved to platelet count of 307 000 k/uL, Hgb 12.2 g/ dL (nadir 9.2 g/dL), haptoglobin 78 mg/dL normalization of LDH and improved creatinine. Atypical HUS is a rare form of TMAwith mutations in C3 noted in 5% of cases. Complement cascade dysfunction leads to endothelial deposits and microvasculature damage. The resulting prothrombotic state causes obstructive microvascular thrombi predominantly affecting the kidneys but can cause multiorgan dysfunction. The SARS-CoV-2 virus may precipitate atypical HUS relapse due to endothelial damage and complement activation further intensified in patients with existing complement aberrations. Plasma exchange remains a standard of care for atypical HUS, as it effectively removes the antibodies and other proteins. Eculizumab a humanized monoclonal IgG antibody binds to complement proteins, preventing cleavage into C5a and C5b blocking C5b-9(MAC) activation. In patients with CFH, CFI, C3, and CFB mutations, eculizumab is the preferred intervention. Copyright © 2023 Southern Society for Clinical Investigation.

Vaporized H2O2 decontamination against surrogate viruses for the reuse of N95 respirators in the COVID-19 emergency (preprint)

Decontamination of N95 respirators has become critical to alleviate PPE shortages for healthcare workers in the current COVID-19 emergency. The factors that are considered for the effective reuse of these masks are the fit, filter efficiency and decontamination/disinfection level both for SARS-CoV-2, which is the causative virus for COVID-19, and for other organisms of concern in the hospital environment such as Staphylococcus aureus or Clostridium difficile. In its guidance entitled 'Recommendations for Sponsors Requesting EUAs for Decontamination and Bioburden Reduction Systems for Surgical Masks and Respirators During the Coronavirus Disease 2019 (COVID19) Public Health Emergency' (May 2020)[1], the FDA recommends a 6-log10 reduction in either the most resistant bacterial spores for the system or in a mycobacterium species to authorize the use of a decontamination method of N95 respirators for single or multiple users. While the goal is primarily inactivation against SARS-CoV-2, testing of decontamination methods against the virus may not always be available. For decontamination methods considered for only single users, the recommendation is a 6-log10 reduction in the infective virus concentration of 3 non-enveloped viruses or in the concentration of two Gram (+) and two Gram (-) bacteria. Based on these recommendations, we explored the efficacy of vaporized H2O2 (VHP) treatment of N95 respirators against surrogate viruses covering a wide range of disinfection resistance for emergency decontamination and reuse to alleviate PPE shortages for healthcare workers in the COVID-19 emergency.

Efficacy of moist heat decontamination against various pathogens for the reuse of N95 respirators in the COVID-19 emergency (preprint)

Decontamination of N95 respirators has become critical to alleviate PPE shortages for healthcare workers in the current COVID-19 emergency. The factors that are considered for the effective reuse of these masks are the fit, filter efficiency and decontamination/disinfection level both for SARS-CoV2, which is the causative virus for COVID-19, and for other organisms of concern in the hospital environment such as Staphylococcus aureus or Clostridium difficile. The efficacy of inactivation or eradication against various pathogens should be evaluated thoroughly to understand the level of afforded disinfection. Methods commonly used in the sterilization of medical devices such as ionizing radiation, vaporized hydrogen peroxide, and ethylene oxide can provide a high level of disinfection, defined as a 6 log10 reduction, against bacterial spores, considered the most resistant microorganisms. CDC guidance on the decontamination and reuse of N95s also includes the use of moist heat (60{degrees}C, 80% relative humidity, 15-30 min) as a possible recommendation based on literature showing preservation of fit efficiency and inactivation of H1N1 on spiked masks. Here, we explored the efficacy of using moist heat under these conditions as a decontamination method for an N95 respirator (3M 1860S, St. Paul, MN) against various pathogens with different resistance; enveloped RNA viruses, Gram (+/-) bacteria, and non-enveloped viruses.

Vapor H2O2 sterilization as a decontamination method for the reuse of N95 respirators in the COVID-19 emergency (preprint)

There are a variety of methods routinely used in the sterilization of medical devices using hydrogen peroxide (H2O2) including vaporization, plasma generation and ionization. Many of these systems are used for sterilization and are validated for bioburden reduction using bacterial spores. Here, we explored the benefits of using vaporized H2O2 (VHP) treatment of N95 respirators for emergency decontamination and reuse to alleviate PPE shortages for healthcare workers in the COVID-19 emergency. The factors that are considered for the effective reuse of these respirators are the fit, the filter efficiency and the decontamination/disinfection level for SARS-CoV-2, which is the causative virus for COVID-19 and other organisms of concern in the hospital environment such as methicillin-resistant Staphylococcus aureus or Clostridium difficile. WE showed that the method did not affect fit or filter efficiency at least for one cycle and resulted in a >6 log reduction in bacterial spores and >3.8 log reduction in the infectious SARS-CoV2 load on N95 respirators.