Introduction: As of February 4, 2021, a total of 530,118 COVID-19 cases were recorded in the Philippines with a fatality rate of 2.1%. Significant morbidity from COVID-19 is caused by hyperinflammation. Hemoperfusion (HP), which adsorbs inflammatory cytokines, has been performed in the Philippine General Hospital (PGH) as an adjunct to management given to COVID-19 patients. Objectives: This study aimed to describe the clinical and laboratory profile, ventilatory support, therapeutic regimens, and outcomes of COVID-19 patients who underwent hemoperfusion in PGH. Methods: The COVID-19 patient electronic database (April to September 2020) of the Division of Nephrology was reviewed and we included patients with COVID-19 who underwent hemoperfusion. Demographic, clinical, and laboratory data as well as therapeutics and outcomes were described. Results: Sixty-six patients with COVID-19 underwent hemoperfusion. The majority were male (59.1%) with an average age of 61.3 years (SD 15). Hypertension was the most common comorbidity (62.1%). Acute kidney injury (AKI) requiring dialysis comprised 28.8% while 33.3% had diagnosed chronic kidney disease (CKD). The majority were critical COVID-19 cases who had acute respiratory distress syndrome (ARDS) (56.1%). The mean baseline inflammatory marker levels (Il-6, CRP, LDH, ferritin) were elevated. Post-HP inflammatory markers decreased except for IL-6 among patients who died. Most patients were mechanically ventilated (54.5%). Steroids were the most common medications administered (71.2%). Mortality occurred in 62.1% of the patients. The average length of hospital stay was 20.8 days (SD 19.5), duration from admission to first HP 5.9 days (SD 5.8), and 15.3 days (SD 17.4) from first HP to death or discharge. Conclusion Our study showed the characteristics of patients with COVID-19 who underwent HP. Majority were hypertensive men in their early 60s with critical COVID-19 disease. The mean inflammatory markers were elevated with a decrease in most markers post-hemoperfusion (except for IL-6 among those who died). Despite this, mortality was still high and the average length of hospital stay was long.
Hemoperfusion ; Hemadsorption ; COVID-19

A neutralization-resistant mutant of Newcastle disease virus (NDV) Kr005 strain belonging to class II genotype VII was generated using a neutralizing monoclonal antibody and its biological effects were assessed. The mutant showed single amino acid substitution (E to K) at position 347 of the hemagglutinin-neuraminidase (HN) protein (E347K mutant). The E347K mutant exhibited marked rounding of the cells and few syncytia in infected chicken embryofibroblast (CEF) cells. The hemadsorption and neuraminidase activities of the E347K mutant of the wild-type virus were 118% and 166%, respectively. The mutant produced a rapid elution pattern whereas the wild type had a slow elution pattern. Growth kinetics studies showed that the E347K mutant produced an 80-times higher yield of extracellular virus in CEF cells compared with the wild-type virus. The time-course virus titer showed a marked increase in mutant-infected cells from 6 h to 12 h post infection (pi), which was consistent with the titer pattern time-course for NA activity. The E347K mutant virus showed a slight decrease in virulence compared to the wild-type virus, but there was no change in pathotype when measured by in vivo pathogenicity testing. These results suggest that an E347K mutation in HN protein might be associated with increased NA activity and subsequent enhancement of virus release from infected cells without change in viral pathotype.
Amino Acid Substitution ; Animals ; Chickens ; Genotype ; Giant Cells ; Hemadsorption ; HN Protein ; Kinetics ; Neuraminidase ; Newcastle Disease ; Newcastle disease virus ; Sprains and Strains ; Viral Load ; Virus Release ; Viruses

We introduced 38 single-point amino acid changes into the hemagglutinin (HA) protein of the reassortmented A/Duck/Mongolia/54/01 (H5N2) strain by a PCR random mutation method. The percentage of amino acid changes on the HA domain that did not abrogate hemadsorption activity was calculated to be 89%. Changes in the amino acids of the HA2 domain were observed to be about half of those in the HA1 domain of these mutants. We assumed that amino acid changes in the HA1 domain afforded more flexibility in maintaining the functions of the HA protein than did those in the HA2 domain. Changes at two positions allowed the mutants to have same characteristics with respect to HA function despite the difference in the substituted amino acid. The results suggested that the effect on hemadsorption activity of an amino acid change on the HA protein primarily depends on the position rather than the species of substituted amino acid. An amino acid change at residue 122 from Trp to Arg and 179 from His to Arg resulted in the loss of hemadsorption activity of the HA protein. Site 122 is near the antibody binding site A, and site 179 is in the receptor binding domain (RBD) of HSHA. So that we suggest residue position 179 or 122 is very important to maintain the structure of RBD or antigenic site of H5HA. Position 4 in HA1 changed from Cys to Arg and position 148 in HA2 changed from Cys to Tyr also resulted in the loss of hemadsorption activity of the HA protein. Cys plays an important role in maintaining the structure of HA protein by means of S-S bonds. 3 potential glycosylation sites (Asn-X-Ser/Thr) were lost in our experiment that did not lose the hemadsorption activity of HA. Some interesting positions need to be analyzed more finely. Some amino acid changes identified in vitro experiment may serve as molecular markers for assessing the pandemic potential of H5N1 field isolates.
Amino Acid Sequence ; Animals ; COS Cells ; Cercopithecus aethiops ; Hemadsorption ; Hemagglutinin Glycoproteins, Influenza Virus ; genetics ; Influenza A Virus, H5N2 Subtype ; genetics ; Molecular Sequence Data ; Mutation