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.

Introduction: Limited data exist on clinical characteristics and outcomes of hospitalized COVID-19 patients in low-middle income countries. We aimed to describe the clinical spectrum and outcomes of hospitalized COVID-19 patients at a tertiary-care center in Karachi, Pakistan. Methodology: We conducted an observational study of adult COVID-19 patients hospitalized between February-June 2020. Patients with a discharge diagnosis of COVID-19 and PCR positivity were included. We created logistic regression models to understand association of clinical characteristics with illness severity and in-hospital mortality. Results: The study population comprised 445 patients [67% males, median age 53 (IQR 40-64) years]. Majority of patients (N = 268; 60%) had ≥ 1 co-morbid [37.5% hypertension, 36.4% diabetes]. In-hospital mortality was 13%. Age ≥ 60 (aOR] =1.92; 95 %CI = 1.23-3.03), shortness of breath (aOR=4.43; 95% CI=2.73-7.22), CRP ≥150mg/L (aOR:1.77; 95% CI=1.09-2.85), LDH ≥ 500 I.U/L (aOR:1.98; 95% CI=1.25-3.16), Neutrophil-to-Lymphocyte ratio (NLR) ≥5 (aOR:2.80; 95%CI = 1.77-4.42) and increase in serum creatinine (aOR:1.32; 95%CI=1.07-1.61) were independently associated with disease severity. Septic shock (aOR: 13.27; 95% CI=3.78-46.65), age ≥ 60 (aOR: 3.26; 95% CI=1.07-9.89), Ferritin ≥ 1500ng/ml (aOR: 3.78; 95% CI=1.21-11.8), NLR ≥ 5 (aOR: 4.04; 95% CI=1.14-14.35) and acute kidney injury (aOR: 5.52; 95% CI=1.78-17.06) were independent predictors of in-hospital mortality. Conclusions: We found multiple predictors to be independently associated with in-hospital mortality, except diabetes and gender. Compared to reports from other countries, the in-hospital mortality among COVID-19 patients was lower, despite a high burden of co-morbidities. Further research is required to explore reasons behind this dichotomy.

There is limited evidence on the efficacy of awake prone positioning (PP) in non-ventilated patients with COVID-19 who have hypoxemia. We, therefore, aim to describe our experience with the use of early proning in awake, non-intubated patients with confirmed COVID-19. In our retrospective observational study, 23 patients with confirmed positive PCR test results for Severe Acute respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and hypoxemia that required oxygen therapy with or without non-invasive ventilation were treated with PP. Patients were classified into mild, moderate and severe COVID-19 disease. There were no targeted number of hours for proning per day and patients were kept in prone position according to their tolerance. The primary outcome measure was the avoidance of intubation and secondary outcomes were in-hospital mortality, length of hospital stays and complications related to PP. The mean (standard deviation) age of our cohort was 54.5 (11.7) years, and the majority were males (21/23, 91.3%). Sixty-one per cent (14/23) of the patients were suffering from severe disease and 82.6% (19/23) had bilateral lung involvement with interstitial infiltrates. Majority of the patients were prone positioned for a median of 6 days (IQR 4 – 8). Only one patient required transfer to ICU for mechanical ventilation and subsequently died due to severe ARDS. All 22 patients showed progressive improvement in oxygen requirement and PF ratio, mostly after 3-5 days of proning. The mean length of hospital stay was 12 days. All patients, except one, were discharged in stable conditions, on room air or on a minimal oxygen requirement of 1-2 liters. No major complication of PP was recorded. Awake prone positioning is a valuable and safe therapeutic adjunct that can be applied in patients with moderate-to-severe COVID-19. It can also be included in the home-based management protocols of COVID-19 to improve patient outcomes and mitigate the burden on health care facilities.

IntroductionCytokine release syndrome in COVID-19 is characterized by hyperinflammation, which manifests as acute respiratory distress syndrome (ARDS), multiorgan failure, and high inflammatory parameters. Tocilizumab, an interleukin 6 (IL-6) antagonist has been used in COVID-19 ARDS with conflicting results from different parts of the world. ObjectiveTo study the treatment outcomes with tocilizumab in patients with COVID-19 ARDS and hyperinflammation using the World Health Organization (WHO) COVID-19 ordinal scale. MethodsAn observational study was conducted from Feb 2020 to May 2020 on COVID-19 ARDS patients with hyperinflammation. ResultsA total of 244 patients with COVID-19 were admitted, out of which 107 had ARDS. Thirty patients had both ARDS and hyperinflammation and received tocilizumab. The mean age was 62.5 years (SD: 13.5) and the majority were male (83%). The mean CRP pre-treatment was 217.5 mg/L and post 48 to 72 hours of tocilizumab treatment was 98.5 mg/L. Twenty-one patients (70%) also received concomitant intravenous (IV) methylprednisolone. Of the 30 patients, seven died and 20 recovered. Ten patients required intensive care unit admission and nine developed nosocomial infections. COVID-19-associated aspergillosis was diagnosed in three patients post tocilizumab treatment. Mortality was significantly higher in patients who developed a nosocomial infection and who required intermittent positive pressure ventilation (IPPV). Posttreatment, clinical improvement was observed in patients who had a median score of 5 on the WHO ordinal scale. ConclusionOur study supports the use of tocilizumab in COVID-19 ARDS patients with a pre-treatment median WHO ordinal severity score of 5 and recommends the monitoring of nosocomial infections and opportunistic infections.

Stenotrophomonas maltophilia is an infrequent cause of acute bacterial meningitis and only a few cases have been reported in the literature. Infection is associated with morbidity and mortality, and its optimal management remains ill-defined. The aim of the current study is to review the management of S. maltophilia meningitis. We described two cases of S. maltophilia meningitis following neurosurgical procedures. The first patient was a 60-year-old female. She was admitted to the hospital with a left basal ganglia bleed and underwent placement of an external ventricular drain for the treatment of hydrocephalus. She developed S. maltophilia meningitis 20 days after surgery. She was successfully treated with a combination of trimethoprimsulfamethoxazole and intravenous colistin and the removal of the drain. She successfully underwent a ventriculoperitoneal (VP) shunt placement at the therapeutic midway point. The second patient was a 35year-old male with a history of intracranial aneurysm bleeding. He had undergone a craniotomy and placement of a ventriculoperitoneal shunt two years previously. His shunt was replaced twice due to blockage. The last replacement had occurred 15 days prior to the development of meningitis. He was treated with a combination of trimethoprim-sulfamethoxazole and ceftazidime (as well as undergoing another shunt replacement) and experienced an excellent recovery. S. maltophilia is a rare but important cause of nosocomial meningitis. It is strongly associated with prior hospitalization and neurosurgical intervention, which is also found in our case series. The management of S. maltophilia meningitis is a therapeutic challenge due to its high resistance to multiple antibiotics. Optimal therapy is based on antimicrobial sensitivity, and the trimethoprim-sulfamethoxazole-based combination has been shown to be successful. The duration of therapy is debatable, but like most gram-negative meningitis infections, therapy lasting up to three weeks appears to be adequate.