Human inherited complete STAT2 deficiency underlies inflammatory viral diseases.

STAT2 is a transcription factor activated by type I and III IFNs. We report 23 patients with loss-of-function variants causing autosomal recessive (AR) complete STAT2 deficiency. Both cells transfected with mutant STAT2 alleles and the patients' cells displayed impaired expression of IFN-stimulated genes and impaired control of in vitro viral infections. Clinical manifestations from early childhood onward included severe adverse reaction to live attenuated viral vaccines (LAV) and severe viral infections, particularly critical influenza pneumonia, critical COVID-19 pneumonia, and herpes simplex virus type 1 (HSV-1) encephalitis. The patients displayed various types of hyperinflammation, often triggered by viral infection or after LAV administration, which probably attested to unresolved viral infection in the absence of STAT2-dependent types I and III IFN immunity. Transcriptomic analysis revealed that circulating monocytes, neutrophils, and CD8+ memory T cells contributed to this inflammation. Several patients died from viral infection or heart failure during a febrile illness with no identified etiology. Notably, the highest mortality occurred during early childhood. These findings show that AR complete STAT2 deficiency underlay severe viral diseases and substantially impacts survival.

Clinical and biochemical characteristics of people experiencing post-coronavirus disease 2019-related symptoms: A prospective follow-up investigation.

Background: Post-acute coronavirus disease 2019 (COVID-19) syndrome, also known as long COVID, is a prolonged illness after the acute phase of COVID-19. Hospitalized patients were known to have persisting symptoms of fatigue, headache, dyspnea, and anosmia. There is a need to describe the characteristics of individuals with post-COVID-19 symptoms in comparison to the baseline characteristics. Purpose: To investigate the clinical and biochemical characteristics of people who recovered from COVID-19 after 6 months of discharge from the hospital. Methods: This was a prospective follow-up investigation of hospitalized and discharged COVID-19 patients. Adult patients admitted to King Saud University Medical City, Riyadh, Saudi Arabia, with laboratory-confirmed COVID-19 and discharged were recruited. The baseline demographic information, comorbidities, vital signs and symptoms, laboratory parameters, COVID-19 therapy, and outcomes were collected from the medical records. Blood samples were collected for cytokines estimation. A detailed interview about signs and symptoms was undertaken during the follow-up. Results: Half of the followed-up people reported experiencing at least one of the COVID-19-related symptoms. The mean blood pressure was found higher in follow-up. People with the symptoms were characterized by low lymphocyte count, lower serum calcium levels, and hyperglycemia compared to people without any post-COVID-19 symptoms. Cytokines IL-8, VEGF, and MCP-1 were higher in people with the most frequent symptoms. Conclusion: People with post-COVID-19 symptoms were characterized by lower lymphocyte count, lower serum calcium levels, and hyperglycemia compared to people without symptoms. Individuals with the most frequent post-COVID-19 symptoms had higher baseline pro-inflammatory, chemotactic, and angiogenic cytokines.

Favipiravir Effectiveness and Safety in Hospitalized Moderate-Severe COVID-19 Patients: Observational Prospective Multicenter Investigation in Saudi Arabia.

Objectives: There are limited data on the efficacy and safety of favipiravir antiviral in coronavirus disease 2019 (COVID-19), particularly in the more progressed disease phase. This study aims to evaluate the favipiravir effect on reducing the length of hospital stay and in-hospital mortality among moderate and severe hospitalized COVID-19 patients. Methods: A prospective, multicenter observational study was conducted that included moderate and severe hospitalized adult COVID-19 patients in four major regions (Riyadh (Riyadh), Eastern (Dammam), Al-Qassem (Buraydah), and Macca (Jeddah) of Saudi Arabia. For the primary outcome of all-cause mortality, a Cox proportional hazard analysis was performed. While the association between favipiravir use and length of hospital stay was determined using adjusted generalized linear model. This study was approved by the Central Institutional Review Board in The Saudi Ministry of Health (MoH) with the approval number IRB # 20-85-M. Results: This study included 598 moderate and severe COVID-19 patients, of whom 156 (26%) received favipiravir. Favipiravir treatment was associated with more extended hospital stays (14 vs. 10 median days, P = 0.034) and higher mortality rate (aHR 3.63; 95% CI 1.06-12.45) compared to no favipiravir regimen. Despite lack of effectiveness, favipiravir use was only associated with higher diarrhea adverse effects (12 vs. 5%, P = 0.002), but it did not affect the renal and liver profiles of patients. Conclusion: Favipiravir was ineffective in reducing the length of hospital stay and in-hospital mortality in patients with moderate and severe COVID-19.

Risk factors and predictors that influence SARS-Cov-2 IgG positivity: A cross-sectional study of blood donors in Riyadh, Saudi Arabia.

OBJECTIVES: To study the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after pandemic's peak and before the vaccine enrollment in Riyadh, Saudi Arabia and further explore predictors for SARS-CoV-2 positivity. METHODS: A cross-sectional study of 515 blood donors from November 22 to December 17, 2020 was conducted at King Saud University Medical City, Riyadh, Saudi Arabia to look at SARS-CoV-2 immunoglobulin G (IgG) positivity. The participants were asked questions about their demographic characteristics, past SARS-CoV-2 infection, SARS-CoV-2-related symptoms and exposures. RESULTS: The seroprevalence in our study was 12.2% (n=63/515). Being a non-citizen was associated with significantly higher seroprevalence (OR 2.10, p=0.02). Participants with history of SARS-CoV-2 exposure or symptoms regardless of SARS-CoV-2 diagnosis had higher SARS-CoV-2 IgG positivity compared to unexposed or asymptomatic participants (OR 2.47, p=0.0008 or 11.19, p=0.0001, respectively). Blood donors who had symptomatic SARS-CoV-2 IgG infection had a higher SARS-CoV-2 IgG positivity rate (OR 5.04, p=0.008) and index value (p=0.003) than the asymptomatic. Of all the reported symptoms, cough (p=0.004) and anosmia (p=0.002) were significant predictors of SARS-CoV-2 IgG. CONCLUSION: The seroprevalence of SARS-CoV-2 among the blood donors in Riyadh, Saudi Arabia is considerably lower than the percentages necessary for herd immunity. Developing SARS-CoV-2-symptoms is the critical factor for higher seropositivity after SARS-CoV-2 exposure.