ABSTRACT
Background: Mitochondrial (mt) dysfunction has been described in acute severe SARS-CoV2 infection. It remains unclear whether the disturbances in mt are also present in post-acute sequelae of COVID-19 (PASC). Method(s): We analyzed cross-sectional data from participants without history of COVID and SARS-CoV2 antibody negative (COVID-), with documented prior COVID and full recovery (COVID+ PASC-), and with prior COVID with PASC as defined by the CDC (COVID+PASC+). Mt respiration was measured from peripheral blood mononuclear cells utilizing the Seahorse XFe96 analyzer. Generalized linear regression was used to compare estimates of mt and non-mt respirations, and unadjusted odds ratios using multinomial logistic regression to assess if mt respiration were associated with PASC. Result(s): For this analysis, 59 participants were enrolled, 71.19% (n=42) had a confirmed COVID-19 diagnosis. The overall mean age was 47.47 +/- 14.86 years, 69.49% (n=41) were females and 33.90% (n=20) were non-white race. There was no difference in demographics between participants with and without COVID (p>=0.72). Amongst all COVID+ participants, 19% (n=11) had hypertension and 8% (n=5) had diabetes. Among all COVID+, the median time between COVID diagnosis and study evaluation was 210 (IQR: 119, 453) days, and 50% (n=21) of COVID+ experienced persistent symptoms consistent with PASC. PASC participants had the highest observed values in non-mt respiration (21.57 +/- 10.77 pmol/min), basal respiration (38.95 +/- 17.58 pmol/min), proton leak (10.41 +/- 3.1), maximal respiration (103.91 +/- 58.63 pmol/min), spare respiratory capacity (64.96 +/- 41.82 pmol/min), and ATP production (28.55 +/-14.85 pmol/min). Basal respiration, ATP production, maximal respiration, and non-mt respiration were highest in PASC compared to COVID- (p<=0.02). There was marginal evidence (p=0.05) of a mean difference (8.09 pmol/min) in ATP production between COVID+PASC+ and COVID+PASC-, without differences in proton leak (p=0.23) or spare respiration capacity (p=0.07). Every unit increase in non-mt respiration, basal respiration, maximal respiration, and ATP production increased the predicted odds of PASC by 10.99, 5.6, 1.6 and 6.2%, respectively (Figure). Conclusion(s): Individuals with PASC are consuming more oxygen and producing more ATP in the PBMCs compared to controls. There also appears to be increased PBMC ATP production between PASC and COVID+. We hypothesize that this may reflect a crucial pathogenic mechanism in PASC that may be associated with ongoing inflammation. (Figure Presented).
ABSTRACT
The COVID-19 pandemic has ravaged the world, caused over 1.8 million deaths in its first year, and severely affected the global economy. Hawai'i has not been spared from the transmission of SARS-CoV-2 in the local population, including high infection rates in racial and ethnic minorities. Early in the pandemic, we described in this journal various technologies used for the detection of SARS-CoV-2. Herein we characterize a 969-bp SARS-CoV-2 segment of the S gene downstream of the receptor-binding domain. At the John A. Burns School of Medicine Biocontainment Facility, RNA was extracted from an oropharyngeal swab and a nasal swab from 2 patients from Hawai'i who were infected with SARS-CoV-2 in August 2020. Following PCR, the 2 viral strains were sequenced using Sanger sequencing, and phylogenetic trees were generated using MEGAX. Phylogenetic tree results indicate that the virus has been introduced to Hawai'i from multiple sources. Further, we decoded 13 single nucleotide polymorphisms across 13 unique SARS-CoV-2 genomes within this region of the S gene, with 1 non-synonymous mutation (P681H) found in the 2 Hawai'i strains. The P681H mutation has unique and emerging characteristics with a significant exponential increase in worldwide frequency when compared to the plateauing of the now universal D614G mutation. The P681H mutation is also characteristic of the new SARS-CoV-2 variants from the United Kingdom and Nigeria. Additionally, several mutations resulting in cysteine residues were detected, potentially resulting in disruption of the disulfide bridges in and around the receptor-binding domain. Targeted sequence characterization is warranted to determine the origin of multiple introductions of SARS-CoV-2 circulating in Hawai'i.