Upregulated type I interferon responses in asymptomatic COVID-19 infection are associated with improved clinical outcome.

Understanding key host protective mechanisms against SARS-CoV-2 infection can help improve treatment modalities for COVID-19. We used a blood transcriptome approach to study biomarkers associated with differing severity of COVID-19, comparing severe and mild Symptomatic disease with Asymptomatic COVID-19 and uninfected Controls. There was suppression of antigen presentation but upregulation of inflammatory and viral mRNA translation associated pathways in Symptomatic as compared with Asymptomatic cases. In severe COVID-19, CD177 a neutrophil marker, was upregulated while interferon stimulated genes (ISGs) were downregulated. Asymptomatic COVID-19 cases displayed upregulation of ISGs and humoral response genes with downregulation of ICAM3 and TLR8. Compared across the COVID-19 disease spectrum, we found type I interferon (IFN) responses to be significantly upregulated (IFNAR2, IRF2BP1, IRF4, MAVS, SAMHD1, TRIM1), or downregulated (SOCS3, IRF2BP2, IRF2BPL) in Asymptomatic as compared with mild and severe COVID-19, with the dysregulation of an increasing number of ISGs associated with progressive disease. These data suggest that initial early responses against SARS-CoV-2 may be effectively controlled by ISGs. Therefore, we hypothesize that treatment with type I interferons in the early stage of COVID-19 may limit disease progression by limiting SARS-CoV-2 in the host.

Clinical features and outcome of COVID-19 positive children from a tertiary healthcare hospital in Karachi.

: As the coronavirus disease 2019 (COVID-19) pandemic continues to evolve, differences in epidemiological and clinical features among pediatrics have been noticed across different countries. We describe the spectrum of COVID-19 in pediatric patients treated in tertiary health care. We conducted a retrospective chart review of pediatric patients admitted to Indus Hospital & Health care network, Korangi campus, Karachi; from April 1st, 2020 to July 31st, 2020. A total of 141 COVID-19 cases were reported, males were 81 (57%) and the median age was 8 (0.3-17) years. Moderate and severe infections were noted in 36(26%), and 17(12%) children respectively. Fever (50%) was the most common clinical feature. The SF ratio less than 264 was significantly associated with severe disease (p < .05). Lab investigations that differed significantly across disease severity groups included IL-6 levels (p < .01) and Prothrombin time (p < .05). Majority of children were advised home isolation 89 (63%), 29 (20.5%) were admitted while mortality was observed in 10 (7%) children. No significant difference was observed between children with and without malignancy. Pre-existing comorbidities are significantly associated with COVID-19 infections among children. Reduced SF ratio, elevated Prothrombin time, and interleukin-6 levels are associated with greater disease severity.

Comparison of Clinical and Diagnostic Features of Pediatric Oncology Patients With or Without COVID-19 Infection: A Retrospective Chart Review.

There is a scarcity of data summarizing the clinical picture, laboratory, and imaging findings and outcome in children with malignancy and coronavirus disease 2019 (COVID-19) infection. This study characterizes a detailed comparison of pediatric oncology patients with and without COVID infection. A retrospective study was conducted at The Indus Hospital, Karachi, from March 2020 to June 2020. Clinical presentation, laboratory and imaging findings, disease severity, and outcome were compared between cohorts. The mean age of children with and without COVID was 8.0±4.9 and 7.4±4.1 years, respectively. Hematologic malignancy comprised the largest number of patients, followed by solid tumors. Lymphocytosis and low neutrophil-lymphocyte ratio was observed in the COVID positive group. Cardiac dysfunction (1.4% vs. 0%), acute respiratory distress syndrome (8% vs. 0%) and lower peripheral capillary oxygen saturation/fraction of inspired oxygen ratio (473 vs. 486) found to be associated with severe disease in COVID positive group (P<0.05). Overall mortality in children with COVID was 6.8% versus 2.7% in children without COVID. Pediatric patients with malignancy have different clinical features and laboratory parameters as compared with children without malignancy. Acute respiratory distress syndrome, absolute lymphocytosis and low neutrophil-lymphocyte ratio is associated with severe disease in children with malignancy and COVID infection. In contrast to adults, biochemical markers and complete blood count parameters do not help recognize COVID infection in pediatric patients with malignancy.

Higher entropy observed in SARS-CoV-2 genomes from the first COVID-19 wave in Pakistan.

BACKGROUND: We investigated the genome diversity of SARS-CoV-2 associated with the early COVID-19 period to investigate evolution of the virus in Pakistan. MATERIALS AND METHODS: We studied ninety SARS-CoV-2 strains isolated between March and October 2020. Whole genome sequences from our laboratory and available genomes were used to investigate phylogeny, genetic variantion and mutation rates of SARS-CoV-2 strains in Pakistan. Site specific entropy analysis compared mutation rates between strains isolated before and after June 2020. RESULTS: In March, strains belonging to L, S, V and GH clades were observed but by October, only L and GH strains were present. The highest diversity of clades was present in Sindh and Islamabad Capital Territory and the least in Punjab province. Initial introductions of SARS-CoV-2 GH (B.1.255, B.1) and S (A) clades were associated with overseas travelers. Additionally, GH (B.1.255, B.1, B.1.160, B.1.36), L (B, B.6, B.4), V (B.4) and S (A) clades were transmitted locally. SARS-CoV-2 genomes clustered with global strains except for ten which matched Pakistani isolates. RNA substitution rates were estimated at 5.86 x10-4. The most frequent mutations were 5' UTR 241C > T, Spike glycoprotein D614G, RNA dependent RNA polymerase (RdRp) P4715L and Orf3a Q57H. Strains up until June 2020 exhibited an overall higher mean and site-specific entropy as compared with sequences after June. Relative entropy was higher across GH as compared with GR and L clades. More sites were under selection pressure in GH strains but this was not significant for any particular site. CONCLUSIONS: The higher entropy and diversity observed in early pandemic as compared with later strains suggests increasing stability of the genomes in subsequent COVID-19 waves. This would likely lead to the selection of site-specific changes that are advantageous to the virus, as has been currently observed through the pandemic.