SARS-CoV-2 genetic diversity and variants of concern in Saudi Arabia.

INTRODUCTION: In December 2019, a new severe acute respiratory syndrome coronavirus, SARS-CoV-2, emerged in China, causing coronavirus disease 2019. The present study investigated genetic profiles and variations of SARS-CoV-2 distributed in different regions of Saudi Arabia to begin to understand the pathogenesis and transmission of SARS-CoV-2 in this country and analyzed associations of these variations with host factors. METHODOLOGY: In total, 774 SARS-CoV-2 genomic sequences obtained and annotated by the Global Initiative on Sharing All Influenza Data (GISAID) were captured and analyzed. RESULTS: The most common SARS-CoV-2 clades in Saudi Arabia were GH followed by O, GR, G, and S. Statistically significant associations were detected between clades and patient outcome. Age, as a host factor, was significantly associated with many variables, including virus geographical location, clade, and patient outcome. The most common variants detected were the NSP12_P323L mutation 94.9%, followed by the D614G mutation (76%) and the NS3_Q57H mutation (71.4%). The concerned variants B.1.1.7, B.1.351, and P.1 were not detected in our population. D614G was associated with higher morbidities than the wild-type virus, including higher rates of death and hospitalization. The NS3_Q57H mutation was the only variant associated with better patient outcome than the wild type. Risk of death was highest with the NSP12_P323L mutation (OR = 1.84; 95% CI = 0.37-9.30) and lowest with the NS3_Q57H mutation (OR = 0.43; 95% CI = 0.25-0.727). CONCLUSIONS: SARS-CoV-2 has evolved uniquely and independently in Saudi Arabia. Our findings provide evidence to begin linking the evolutionary implications to host factors and their effects on the virus severity and transmission.

Serum ß2-microglobulin levels in Coronavirus disease 2019 (Covid-19): Another prognosticator of disease severity?

ß2-microglobulin (ß2-m), a 11.8 kDa protein, pairs non-covalently with the α3 domain of the major histocompatibility class (MHC) I α-chain and is essential for the conformation of the MHC class I protein complex. Shed ß2-m is measurable in circulation, and various disorders are accompanied by increases in ß2-m levels, including several viral infections. Therefore, we explored whether ß2-m levels could also be elevated in Coronavirus disease 2019 (Covid-19) and whether they predict disease severity. Serum ß2-m levels were measured in a cohort of 34 patients infected with SARS-CoV-2 on admission to a tertiary care hospital in Riyadh, Saudi Arabia, as well as in an approximately age-sex matched group of 34 uninfected controls. Mean ß2-m level was 3.25±1.68 mg/l (reference range 0.8-2.2 mg/l) in patients (mean age 48.2±21.6) and 1.98±0.61 mg/l in controls (mean age 48.2±21.6). 17 patients (mean age 36.9± 18.0) with mean ß2-m levels of 2.27±0.64 mg/l had mild disease by WHO severity categorization, 12 patients (mean age 53.3±18.1) with mean ß2-m levels of 3.57±1.39 mg/l had moderate disease, and five patients (of whom 2 died; mean age 74.4±13.8) with mean ß2-m levels of 5.85±1.85 mg/l had severe disease (P < = 0.001, by ANOVA test for linear trend). In multivariate ordinal regression ß2-m levels were the only significant predictor of disease severity. Our findings suggest that higher ß2-m levels could be an early indicator of severity of disease and predict outcome of Covid-19. As the main limitations of the study are a single-center study, sample size and ethnicity, these results need confirmation in larger cohorts outside the Arabian Peninsula in order to delineate the value of ß2-m measurements. The role of ß2-m in the etiology and pathogenesis of severe Covid-19 remains to be elucidated.

Diffuse necrotising leukoencephalopathy with microhaemorrhages in a patient with severe COVID-19 disease.

A wide range of neurological complications of coronavirus disease 2019 (COVID-19) is increasingly recognised. Although the majority of these remain ischaemic and haemorrhagic events, various disorders are being reported. In particular, several cases of diffuse acute leukoencephalopathy have been observed in critically ill patients with COVID-19 disease. We report the case of a 59-year-old man with multiple comorbidities and severe COVID-19 pneumonia who developed a diffuse leukoencephalopathy with microhaemorrhages and extensive associated white matter necrosis. Although this is the first documented case of extensive COVID-19-associated white matter necrosis, we highlight the relatively constant features of this injury similar to previously reported cases, including symmetrical involvement of the supratentorial white matter, sparing of the peripheral subcortical regions except in the precentral gyri, frequently associated microhaemorrhages, relative sparing of the deep gray matter structures and infratentorial structures, and lack of enhancement.