COVID-19 viral load not associated with disease severity: findings from a retrospective cohort study

Background: Being able to use COVID-19 RT-PCR Ct values as simple clinical markers of disease outcome or prognosis would allow for the easy and proactive identification and triaging of high-risk cases. This study's objective was thus to explore whether a correlation exists between COVID-19 viral loads, as indicated by RT-PCR Ct values, and disease severity, as indicated by respiratory indices.Results: A multi-centre cross-sectional retrospective study was conducted, using data obtained from Bahrain's National COVID-19 Task force's centralised database. The study period ranged from May 2, 2020 to July 31, 2020. A multivariable logistic regression was used to assess for a correlation using data from a total of 1057 admitted COVID-19 cases. The covariates adjusted for included sex, age, presentation, and comorbidities. In our cohort, Ct value showed no statistical significance for an association with requirement for oxygenation on admission (Odds ratio 1.046; 95%CI 0.999 to 1.096, p = 0.054).Conclusion: Viral load, as indicated by Ct values, did not seem to be associated with requirement for oxygenation on admission in our cohort. We postulate however that time since onset of symptom may have acted as an unaccounted-for confounder. As such, RT-PCR Ct values may not be a useful prognostic clinical tool in isolation.</p

Anticoagulation in COVID-19

As hospitals worldwide continue to admit an influx of coronavirus disease 2019 (COVID-19) patients, the puzzling pathogenesis behind the witnessed mortality rates is progressively being pieced together. Aside from the established respiratory involvement, the cardiac system has recently been implicated, albeit with controversial mechanisms. New data from cohort studies and autopsies suggest a potential role for coagulopathy in COVID-19. Although the exact mechanism may likewise remain controversial, several clinical implications are now imperative for discussion

Vaccine trials during a pandemic: potential approaches to ethical dilemmas

Ever since the emergence of the coronavirus disease 2019 (COVID-19), global public health infrastructures and systems, along with community-wide collaboration and service, have risen to an unprecedented challenge. Vaccine development was immediately propelled to the centre of all our scientific, public health and community efforts. Despite the development of SARS-CoV-2 vaccines arguably being the greatest and most palpable achievements of the past 12 months, they have also been one of the most contentious and debated issues during the pandemic. However, what uniquely differentiates vaccine development is its intimate relationship with the community it seeks to serve; both in its clinical trial testing as an efficacious and safe prophylactic, and its post-developmental 'roll-out' success, as an effective public health tool. These relationships have birthed a myriad of complexities, from community-based mistrust, to academically contended ethical dilemmas. Indeed, the accelerated advances in the COVID-19 vaccine race have further exacerbated this phenomenon, bringing with it new ethical dilemmas that need to be examined to ensure the continued clinical success of these therapeutics and a renewed societal trust in clinical medicine.In this paper, we discuss two major ethical dilemmas: (1) the equipoise of continuing new vaccine trials in the advent of successful candidates and (2) the maleficence of blinded placebo arms. Accordingly, we discuss six different potential approaches to these ethical dilemmas: (1) continuing with placebo-controlled trials, (2) transitioning from placebo-controlled to open-label, (3) unblinding at-risk priority groups only, (4) transitioning to a blinded stepped-wedge cross-over design, (5) progressing to a blinded active-controlled stepped-wedge cross-over trial, and (6) conducting randomised stepped-wedge community trials. We also propose a decision-making algorithm for relevant stakeholders in advanced stages of vaccine trials.It is important to remember that the emergent nature of the COVID-19 situation does not justify a compromise on core ethical values. In fact, the discourse surrounding this topic and the decisions made will remain a potent case study and a continuously referenced example for all such future scenarios

Evaluation of rapid antigen tests using nasal samples to diagnose SARS-CoV-2 in symptomatic patients

Introduction: The best way to mitigate an outbreak besides mass vaccination is via early detection and isolation of infected cases. As such, a rapid, cost-effective test for the early detection of COVID-19 is required.Methods: The study included 4,183 mildly symptomatic patients. A nasal and nasopharyngeal sample obtained from each patient was analyzed to determine the diagnostic ability of the rapid antigen detection test (RADT, nasal swab) in comparison with the current gold-standard (RT-PCR, nasopharyngeal swab).Results: The calculated sensitivity and specificity of the RADT was 82.1 and 99.1%, respectively. Kappa's coefficient of agreement between the RADT and RT-PCR was 0.859 (p Conclusion: Our study's results support the potential use of nasal swab RADT as a screening tool in mildly symptomatic patients, especially in patients with higher viral loads.</p

Characteristics of patients with SARS-CoV-2 positive cerebrospinal fluid: a systematic review

Background: The coronavirus disease 2019 (COVID-19) has been shown to affect several systems, notably the respiratory system. However, there has been considerable evidence implicating the nervous system in COVID-19 infection. This study aims to investigate the clinical characteristics of patients whose cerebrospinal fluid (CSF) tested positive for SARS-CoV-2.Methods: A comprehensive search of PubMed, EMBASE, Scopus, WHO Coronavirus database, bioRxiv, medRxiv, and Web of Science databases was carried out in August 2020. Original studies involving patients who tested positive for SARS-COV-2 in their CSF were included. Key search terms encompassed all variations of "COVID-19" AND "Cerebrospinal Fluid".Results: A total of 525 studies were identified. Fifty-six full-text articles were assessed, of which 14 were included. In total, 14 patients tested positive for SARS-CoV-2 in their CSF. 21.4% (3/14) of patients had negative nasopharyngeal (NP) swabs despite a positive CSF sample. About 14.2% (2/14) of patients who initially had positive NP swabs developed neurological deterioration after a supposed recovery as indicated by their negative NP swabs, but their CSF still tested positive for SARS-CoV-2. Common symptoms were headache (42.8%; 6/14), fever (35.6%; 5/14), vomiting (28.6%; 4/14), cough (28.6; 4/14), visual disturbances (28.6%; 4/14), diarrhea (21.4%; 3/14), and seizures (21.4%; 3/14). Four patients (28.6%) were admitted to ICU, one (7.14%) was admitted to a rehabilitation facility, and two (14.3%) died.Conclusion: Physicians should be familiar with the presenting neurological features of COVID-19, and be aware that they can occur despite a negative NP swab. The results of this study are intended to aid in the development of informed guidelines to diagnose and treat COVID-19 patients with neurological manifestations.</div

Thrombotic events following tocilizumab therapy in critically ill COVID-19 patients: a Façade for prognostic markers

Background: Hospitals in the Middle East Gulf region have experienced an influx of COVID-19 patients to their medical wards and intensive care units. The hypercoagulability of these patients has been widely reported on a global scale. However, many of the experimental treatments used to manage the various complications of COVID-19 have not been widely studied in this context. The effect of the current treatment protocols on patients' diagnostic and prognostic biomarkers may thus impact the validity of the algorithms adopted.Case presentation: In this case series, we report four cases of venous thromboembolism and 1 case of arterial thrombotic event, in patients treated with standard or intensified prophylactic doses of unfractionated heparin or low molecular weight heparin at our institution. Tocilizumab has been utilized as an add-on therapy to the standard of care to treat patients with SARS-CoV-2 associated acute respiratory distress syndrome, in order to dampen the hyperinflammatory response. It is imperative to be aware that this drug may be masking the inflammatory markers (e.g. IL6, CRP, fibrinogen, and ferritin), without reducing the risk of thrombotic events in this population, creating instead a façade of an improved prognostic outcome. However, the D-dimer levels remained prognostically reliable in these cases, as they were not affected by the drug and continued to be at the highest level until event occurrence.Conclusions: In the setting of tocilizumab therapy, traditional prognostic markers of worsening infection and inflammation, and thus potential risk of acute thrombosis, should be weighed carefully as they may not be reliable for prognosis and may create a façade of an improved prognostic outcome insteasd. Additionally, the fact that thrombotic events continued to be observed despite decrease in inflammatory markers and the proactive anticoagulative approach adopted, raises more questions about the coagulative mechanisms at play in COVID-19, and the appropriate management strategy.</p

Outcome measures in neurosurgery: is a unified approach better? A literature review

Background: Accurate assessment and evaluation of health interventions are crucial to evidence-based care. The use of outcome measures in neurosurgery grew with the introduction of the Glasgow Coma Scale. Since then, various outcome measures have appeared, some of which are disease-specific and others more generally. This article aims to address the most widely used outcome measures in three major neurosurgery subspecialties, "vascular, traumatic, and oncologic," focusing on the potential, advantages, and drawbacks of a unified approach to these outcome measures. Methods: A literature review search was conducted by using PubMed MEDLINE and Google scholar Databases. Data for the three most common outcome measures, The Modified Rankin Scale (mRS), The Glasgow Outcome Scale (GOS), and The Karnofsky Performance Scale (KPS), were extracted and analyzed. Results: The original objective of establishing a standardized, common language for the accurate categorization, quantification, and evaluation of patients' outcomes has been eroded. The KPS, in particular, may provide a common ground for initiating a unified approach to outcome measures. With clinical testing and modification, it may offer a simple, internationally standardized approach to outcome measures in neurosurgery and elsewhere. Based on our analysis, Karnofsky's Performance Scale may provide a basis of reaching a unified global outcome measure. Conclusion: Outcome measures in neurosurgery, including mRS, GOS, and KPS, are widely utilized assessment tools for patients' outcomes in various neurosurgical specialties. A unified global measure may offer solutions with ease of use and application; however, there are limitations.</p

COVID-19: breaking down a global health crisis

Coronavirus disease 2019 (COVID-19) is the second pandemic of the twenty-first century, with over one-hundred million infections and over two million deaths to date. It is a novel strain from the Coronaviridae family, named Severe Acute Respiratory Distress Syndrome Coronavirus-2 (SARS-CoV-2); the 7th known member of the coronavirus family to cause disease in humans, notably following the Middle East Respiratory syndrome (MERS), and Severe Acute Respiratory Distress Syndrome (SARS). The most characteristic feature of this single-stranded RNA molecule includes the spike glycoprotein on its surface. Most patients with COVID-19, of which the elderly and immunocompromised are most at risk, complain of flu-like symptoms, including dry cough and headache. The most common complications include pneumonia, acute respiratory distress syndrome, septic shock, and cardiovascular manifestations. Transmission of SARS-CoV-2 is mainly via respiratory droplets, either directly from the air when an infected patient coughs or sneezes, or in the form of fomites on surfaces. Maintaining hand-hygiene, social distancing, and personal protective equipment (i.e., masks) remain the most effective precautions. Patient management includes supportive care and anticoagulative measures, with a focus on maintaining respiratory function. Therapy with dexamethasone, remdesivir, and tocilizumab appear to be most promising to date, with hydroxychloroquine, lopinavir, ritonavir, and interferons falling out of favour. Additionally, accelerated vaccination efforts have taken place internationally, with several promising vaccinations being mass deployed. In response to the COVID-19 pandemic, countries and stakeholders have taken varying precautions to combat and contain the spread of the virus and dampen its collateral economic damage. This review paper aims to synthesize the impact of the virus on a global, micro to macro scale

COVID-19 versus SARS: a comparative review

The two genetically similar severe acute respiratory syndrome coronaviruses, SARS-CoV-1 and SARS-CoV-2, have each been responsible for global epidemics of vastly different scales. Although both viruses arose from similar origins, they quickly diverged due to differences in their transmission dynamics and spectrum of clinical presentations. The potential involvement of multiple organs systems, including the respiratory, cardiac, gastrointestinal and neurological, during infection necessitates a comprehensive understanding of the clinical pathogenesis of each virus. The management of COVID-19, initially modelled after SARS and other respiratory illnesses, has continued to evolve as we accumulate more knowledge and experience during the pandemic, as well as develop new therapeutics and vaccines. The impact of these two coronaviruses has been profound for our health care and public health systems, and we hope that the lessons learned will not only bring the current pandemic under control, but also prevent and reduce the impact of future pandemics

Safety and efficacy of COVID-19 prime-boost vaccinations: homologous BBIBP-CorV versus heterologous BNT162b2 boosters in BBIBP-CorV-primed individuals

Background: Booster vaccine doses against SARS-CoV-2 have been advocated to address evidence of waning immunity, breakthrough infection, and the emergence of immune-evasive variants. A heterologous prime-boost vaccine strategy may offer advantages over a homologous approach, but the safety and efficacy of this approach with the mRNA vaccine BNT162b2 (BNT: Pfizer) and inactivated BBIBP-CorV (BBIBT: Sinopharm) vaccines have not been studied. Methods: We conducted a non-randomized, non-blinded phase II observational community trial across Bahrain, investigating the reactogenic and immunogenic response of participants who had previously received two doses of BBIBP, followed by a third booster dose of either BBIBP (homologous booster) or BNT (heterologous booster). Immunogenicity through serological statuswas determined at baseline and on the following 8th week. Reactogenicity data (safety and adverse events) were collected throughout study period, in addition to participant-led electronic journaling. Results: 305 participants (152 BBIBP and 153 BNT booster) were enrolled in the study,with 246 (127 BBIBP and 119 BNT booster) included in the final analysis. There was a significant increase in anti-SARS-CoV-2 antibody levels post booster administration in both groups; however, the heterologous BNT arm demonstrated a significantly larger mean increase in the level of spike (S) antigen-specific antibodies (32.7-fold increase versus 2.6, p Conclusion: Heterologous prime-boost vaccination with the mRNA BNT162b2 (Pfizer) vaccine in those who had received two doses of inactivated virus BBIBP-CorV (Sinopharm) vaccine demonstrated a more robust immune response against SARS-CoV-2 than the homologous BBIBP booster and appears safe and well tolerated. Clinical Trial Registry Number (ClinicalTrials.gov): NCT04993560.</p