Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-COVID Syndrome: A Common Neuroimmune Ground? (preprint)

A Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown aetiology under growing interest now in view of the increasingly recognized post-COVID syndrome as a new entity with similar clinical presentation. We performed the first cross-sectional study of ME/CFS in community population in Russia and then described and compared some clinical and pathophysiological characteristics of ME/CFS and post-COVID syndrome as neuroimmune disorders. Of the cohort of 76 individuals who suggested themselves suffering from ME/CFS 56 subsequently were confirmed as having CFS/ME according to ≥1 of the 4 most commonly used case definition. Of the cohort of 14 individuals with post-COVID-19 syndrome 14 met diagnostic criteria for ME/CFS. The prevalence of clinically expressed and subclinical anxiety and depression in ME / CFS and post-COVID ME/CFS did not differ significantly from that in healthy individuals. Severity of anxiety / depressive symptoms did not correlate with the severity of fatigue neigther in ME / CFS nor in post-COVID ME/CFS, but the positive correlation was found between the severity of fatigue and 20 other symptoms of ME / CFS related to the domains of “post-exertional exhaustion”, “immune dysfunction”, “sleep disturbances”, "dysfunction of the autonomic nervous system", "neurological sensory / motor disorders" and "pain syndromes". Immunological abnormalities were identified in 12/12 patients with ME / CFS according to the results of laboratory testing. The prevalence of postural orthostatic tachycardia assessed by the active standing test was 37.5% in ME / CFS and 75.0% in post-COVID ME/CFS (the latter was higher than in healthy controls, p = 0.02) There was a more pronounced increase in heart rate starting from the 6th minute of the test in post-COVID ME/CFS compared with the control group. Assessment of the functional characteristics of microcirculation by laser doppler flowmetry revealed obvious and very similar changes in ME/CFS and post-COVID ME/CFS compared to the healthy controls. The identified pattern corresponded to the hyperemic form of microcirculation disorders, usually observed in acute inflammatory processes or in deficiency of systemic vasoconstriction influences.

Sensitivity of pregnancy field on the COVID-19 case report form among pregnancies completed through December 31, 2020 — Illinois and Tennessee (preprint)

Introduction: The considerable volume of infections from SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), has made it challenging for health departments to collect complete data for national disease reporting. We sought to examine sensitivity of the COVID-19 case report form (CRF) pregnancy field by comparing CRF data to the gold standard of CRF data linked to birth and fetal death certificates. Methods: CRFs for women aged 15–44 years with laboratory-confirmed SARS-CoV-2 infection were linked to birth and fetal death certificates for pregnancies completed during January 1–December 31, 2020 in Illinois and Tennessee. Among linked records, pregnancy was considered confirmed for women with a SARS-CoV-2 specimen collection date on or prior to the delivery date. Sensitivity of the COVID-19 CRF pregnancy field was calculated by dividing the number of confirmed pregnant women with SARS-CoV-2 infection with pregnancy indicated on the CRF by the number of confirmed pregnant women with SARS-CoV-2 infection. Results: Among 4,276 (Illinois) and 2,070 (Tennessee) CRFs that linked with a birth or fetal death certificate, CRF pregnancy field sensitivity was 45.3% and 42.1%, respectively. In both states, sensitivity varied significantly by maternal race/ethnicity, insurance, trimester of prenatal care entry, month of specimen collection, and trimester of specimen collection. Sensitivity also varied by maternal education in Illinois but not in Tennessee. Discussion: Sensitivity of the COVID-19 CRF pregnancy field varied by state and demographic factors. To more accurately assess outcomes for pregnant women, jurisdictions might consider utilizing additional data sources and linkages to obtain pregnancy status.

Altered Transcript Levels of Cytokines in COVID-19 Patients (preprint)

The pandemic caused by severe acute respiratory syndrome coronavirus 2 and the related disorder i.e. “coronavirus disease 2019” (COVID-19) have encouraged researchers to unravel the molecular mechanism of disease severity. Several lines of evidence support the impact of "cytokine storm" in the pathogenesis of severe forms of the disorder. We aimed to assess the expression levels of nine cytokine coding in COVID-19 patients admitted in a hospital. Expression levels of IFN-G, IL-2, IL-4, IL-6, IL-17, TGF-B, IL-8 and IL-1B were significantly higher in COVID-19 patients compared with healthy controls and in both female and male patients compared with sex-matched controls. However, expression of none of these cytokines was different between ICU-admitted patients and other patients except for IL-6 whose expression was lower in the former group compared with the latter (ratio of means = 0.33, P value = 4.82E-02). Expression of TNF-A was not different between COVID-19 patients and healthy controls. Then, we assessed diagnostic power of cytokine coding genes in differentiating between COVID-19 patients and controls. The area under curve (AUC) values range from 0.94 for IFN-G to 1.0 for IL-2 and IL-1B. After combining the transcript levels of all cytokines, AUC, sensitivity and specificity values reached 1.0, 1.0 and 0.99, respectively. For differentiation between ICU-admitted patients and other patients, IL-4 with AUC value of 0.68, had the best diagnostic power among cytokine coding genes. Expression of none of cytokine coding genes was correlated with the assessed clinical/demographic data including age, gender, ICU admission, or CRP/ESR levels. Our study provides further evidence for contribution of “cytokine storm” in the pathobiology of moderate/severe forms of COVID-19.