In a recent study posted to the medRxiv* preprint server, researchers explored post-illness gut-microbiome and metabolomic profiles of community coronavirus disease 2019 (COVID-19) cases and individuals with non-COVID-19 illnesses of prolonged duration.
Studies have reported several cases of mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections managed in the communities; however, severe COVID-19 cases have been reported among persons prone to cardiovascular illness. There have been growing concerns over the long duration of COVID-19 symptoms in many persons, including those cases managed in communities. However, risk factors and biological variables associated with prolonged COVID-19 symptom duration have not been well-characterized.
About the study
In the present study, researchers investigated if metabolomic profiles of community-residing persons differed from those with varying duration of COVID-19 symptoms.
The team also investigated if the composition of the fecal microbiome obtained post-acute illness differed between persons with diseases of varying duration of symptoms with or without prior COVID-19 history. Furthermore, the team assessed the probable association between the gut metagenomic composition and metabolomic profiles of the study participants.
Participants of the CSSB (COVID symptom study biobank) study were recruited and categorized as (i) asymptomatic COVID-19 group; (ii) short COVID-19 duration (≤2 weeks); (iii) long COVID-19 duration (≥28 days); and (iv) long symptom duration (≥28 days) of non-COVID-19 illnesses. Long COVID groups were recategorized as OCS28 (28 to 83 days) and post-COVID-19 syndrome (PCS84, >84 days).
The same parameters were applied for non-COVID-19 illnesses, and six groups were formed comprising four COVID-19 groups as (i) asymptomatic; (ii) acute COVID-19 (≤1 week); (iii) PCS84, and (iv) OSC28; and two non-COVID-19 groups: non-COVID-19 illnesses for 28-83 days (NC28), non-COVID-19 illnesses for ≥84 days (NC84).
Capillary blood samples and fecal samples were obtained between November 2020 and January 2021 from all and a few participants, respectively. Nuclear magnetic resonance metabolomic analysis of metabolites (n=249, of which 37 were clinically validated) associated with COVID-19-associated hospitalization was performed in March/April 2021.
Genomic deoxyribonucleic acid (gDNA) was extracted, following which DNA libraries were prepared and sequenced, and metagenomic analysis was performed. Generalized linear modeling was used, and spearman correlation coefficients were calculated after controlling for confounding variables to determine the association between the microbiome profiles and metabolome profiles of the study participants, and the infectious diseases risk prediction (ID) scores were evaluated.
Of 15,564 persons who received email invites for the CSSB study, 37% (n=5694) were recruited for the present study, of which 84% (n=4787) of participants returned their samples for analyzing their metabolomic profiles. The average age of the participants was 53 years, most of them (79%) were women, adequate data were obtained for 78% (n=3718) individuals, and 81% (n=2561) could be phenotypically categorized.
The levels of 36% (n=90/246) metabolites were different among the OSC28 group and the asymptomatic COVID-19 group, of which 43% (n=39) differed among the NC28 group and the asymptomatic COVID-19 group. Of the 37 clinically validated metabolites, fatty acid levels differed among asymptomatic COVID-19 cases and the symptomatic COVID-19 and non-COVID-19 participants.
Higher polyunsaturated fatty acids (PUFA) levels were associated with lesser chances of longer COVID-19 duration (OR= 0.7 for OSC28 versus asymptomatic cases) and non-SARS-CoV-2 illnesses (OR=0.7 for NC28 versus asymptomatic). The monounsaturated fatty acids (MUFA) levels were associated with prolonged COVID-19 (OR=1.3 for OSC28 versus asymptomatic SARS-CoV-2 infection), and elevated triglycerides (TG) and very low-density lipoproteins (VLDL) were related to prolonged illnesses in COVID-19 and non-COVID-19 participants.
TG to phosphoglycerides ratios were also directly proportional to the duration of illness. Contrastingly, elevated high-density lipoprotein (HDL) levels were related to asymptomatic COVID-19 cases. Neither glycoprotein acetyls nor amino acid levels were related to the duration of COVID-19 symptoms. Only 2.8% (n=7) variables significantly differed among long COVID groups (PCS84 and OSC28 combined) in comparison to non-COVID-19 illness groups (NC84 and NC28 combined).
Higher HDL values were noted for acute COVID-19 patients (OR 1.2) compared to non-COVID-19 illness patients, with even greater levels among the asymptomatic illness group (OR 1.4) compared to non-COVID-19 illnesses. Greater ID scores were associated with prolonged symptom durations, and the impact of ID scores was slightly stronger post- hPDI (healthy plant-based diet index) adjustments with ORs 1.6 and 1.5 with and without hPDI, respectively (OSC28 vs. asymptomatic COVID-19).
Microbial richness was not significantly different among the metabolomic subset persons (n=301), except for species such as Streptococcus vestibularis, Firmicutes bacterium CAG 94 Ruminococcus callidus, and an atherogenic-dyslipidaemic profile was associated with a prolonged duration of COVID-19 and non-COVID-19 illnesses. No significant associations were found between the duration of illness and the microbiome of the gut among convalescents.
Overall, the study findings highlighted the potential role of cardiometabolic dysfunction in the experience of long illness duration, including after COVID-19.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.