A Review of Candidate Therapies for Beta Coronavirus a Molecular Research

Coronavirus disease 2019 (COVID-19) is an infectious illness caused by the coronavirus 2 that causes severe acute respiratory illness (SARS-CoV-2). The first instance of this virus was reported on November 17th, 2019 in Wuhan, China. The COVID-19 outbreak is evidenced with devastating consequences such as 34.9% rate of mortality in 27 countries. The metastasizing of COVID-19 all over the world is alarmed to cause significant losses of human life, and for this there is no specific vaccination or therapy for COVID-19 in particular. The therapies suggested at this time are adapted from the treatments of Severe Acute Respiratory Syndrome (SARV-CoV). For instance, the development for a particular therapy or vaccination for COVID-19 is an urgent requirement. The pattern of study is based on investigating the research papers for the period of 2012-2020, identifying all the potential aspects of medical research contributing for the development of treatment against diverse families of coronavirus. By analyzing this approach, this study is aimed to provide a directed approach for developing appropriate therapy for COVID-19.

Patient perceptions of infectious illnesses preceding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Objectives Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is often reported to be caused by an infectious agent. However, it is unclear whether one infectious agent might be the cause or whether there might be many different infectious agents. The objective of this study was to identify self-reported infectious illnesses associated with the onset of ME/CFS. Methods The present study involved data from multiple sites in several countries. 1773 individuals diagnosed with either ME, CFS or ME/CFS provided qualitative data concerning infectious triggers which were coded and classified for analysis. Results 60.3% of patients report a variety of infectious illnesses some time before onset of ME/CFS. The most frequently reported infectious illness was Mononucleosis, which occurred in 30% of infections. However, over 100 other infectious illnesses were mentioned. Discussion The findings suggest that many infectious agents might be associated with the onset of ME/CFS.

Severe bilateral pleuropneumonia caused by Legionella sainthelensi: a case report

Background Legionella spp. are ubiquitous freshwater bacteria responsible for rare but potentially severe cases of Legionnaires’ disease (LD). Legionella sainthelensi is a non-pneumophila Legionella species that was first isolated in 1980 from water near Mt. St-Helens (USA). Although rare cases of LD caused by L. sainthelensi have been reported, very little data is available on this pathogen. Case presentation We describe the first documented case of severe bilateral pleuropneumonia caused by L. sainthelensi. The patient was a 35-year-old woman with Sharp’s syndrome treated with long-term hydroxychloroquine and corticosteroids who was hospitalized for an infectious illness in a university hospital in Reunion Island (France). The patient’s clinical presentation was complicated at first (bilateral pneumonia, multiloculated pleural effusion, then bronchopleural fistula) but her clinical condition eventually improved with the reintroduction of macrolides (spiramycin) in intensive care unit. Etiological diagnosis was confirmed by PCR syndromic assay and culture on bronchoalveolar lavage. Conclusions To date, only 14 documented cases of L. sainthelensi infection have been described worldwide. This pathogen is difficult to identify because it is not or poorly detected by urinary antigen and molecular methods (like PCR syndromic assays that primarily target L. pneumophila and that have only recently been deployed in microbiology laboratories). Pneumonia caused by L. sainthelensi is likely underdiagnosed as a result. Clinicians should consider the possibility of non-pneumophila Legionella infection in patients with a compatible clinical presentation when microbiological diagnostic tools targeted L. pneumophila tested negative.

Navigating uncertain illness trajectories for young children with serious infectious illness: a mixed-methods modified grounded theory study.

Infectious illness is the biggest cause of death in children due to a physical illness, particularly in children under five years. If mortality is to be reduced for this group of children, it is important to understand factors affecting their pathways to hospital. The aim of this study was to retrospectively identify organisational and environmental factors, and individual child, family, and professional factors affecting timing of admission to hospital for children under five years of age with a serious infectious illness (SII). Methods An explanatory modified grounded theory mixed methods design was used in collaboration with parents. Two stages of data collection were conducted: Stage 1, interviews with 22 parents whose child had recently been hospitalised with a SII and 14 health professionals (HPs) involved in their pre-admission trajectories; Stage 2, focus groups with 18 parents and 16 HPs with past experience of SII in young children. Constant comparative analysis generated the explanatory theory. Findings The core category was Navigating uncertain illness trajectories for young children with serious infectious illness. Uncertainty was prevalent throughout the parents and HPs stories about their experiences of navigating social rules and overburdened health services for these children. The complexity of and lack of continuity within services, family lives, social expectations and hierarchies provided the context and conditions for childrens, often complex, illness trajectories. Parents reported powerlessness and perceived criticism leading to delayed help-seeking. Importantly, parents and professionals missed symptoms of serious illness. Risk averse services were found to refer more children to emergency departments. Conclusions Parents and professionals have difficulties recognising signs of SII in young children and can feel socially constrained from seeking help. The increased burden on services has made it more difficult for professionals to spot the seriously ill child.

Association of the CPT1A p.P479L Metabolic Gene Variant With Childhood Respiratory and Other Infectious Illness in Nunavut

Objective: Infectious illness, including lower respiratory tract infection (LRTI), is a leading cause of childhood morbidity and infant mortality in Inuit children in Nunavut Canada. The carnitine palmitoyltransferase 1A (CPT1A) p.P479L variant is common in arctic Indigenous populations of Alaska, Canada, and Greenland. CPT1A is a fatty acid oxidation enzyme expressed in the liver, immunocytes and other tissues, and is needed to use fats for energy during fasting. Previous association of the variant with early childhood infectious illness and infant death has been challenged because of sample size and limited adjustment for confounders. We evaluated whether the p.P479L variant is associated with infectious illness in Inuit children of Nunavut, Canada.Methods: We conducted a retrospective clinical chart review of 2,225 Inuit children (0–5 years) for infectious illness (including otitis media, gastroenteritis, and hospital admission for LRTI), prenatal, perinatal, and socioeconomic indicators, subsequently linking to CPT1A genotype. Multivariable logistic regression adjusted for birth characteristics, breastfeeding, maternal smoking, food insecurity, and socioeconomic indicators.Results: Overall, 27% of children were hospitalized for LRTI, 86% had otitis media and 50% had gastroenteritis. The p.P479L allele frequency was 0.82. In multivariable analysis, p.P479L homozygosity was associated with LRTI admission (aOR:2.88 95%CI:1.46–5.64), otitis media (aOR:1.83, 95%CI:1.05–3.21), and gastroenteritis (aOR:1.74, 95%CI:1.09–2.77), compared to non-carriers.Conclusion: Children homozygous for the p.P479L variant were more likely to experience infectious illness than non-carriers, including hospitalization for respiratory tract infections. Given the role of CPT1A in immunocytes, our findings indicate that more study is needed to determine if there is a role of the variant in immune response. Continued Inuit involvement is essential when considering next steps.

Corticosterone Enhances Formation of Neutral but Not Fear Memory During Infectious Illness

Survivors of critical illness often report traumatic memories of their illness period, and these memories are thought to contribute to development of neuropsychiatric disorders, such as PTSD. Many patients are treated with high doses of glucocorticoids for their vasoactive and anti-inflammatory properties, and glucocorticoids have also been shown to prevent the development of PTSD after trauma. Due to their activity in the hippocampus and amygdala, the putative protective effect of glucocorticoids may occur via memory formation during illness. To examine the effect of glucocorticoids on memory formation during acute infectious illness, male and female C57BL/6 mice (N=80, 40 male/40 female) underwent cecal ligation and puncture and were treated with either corticosterone (16 mg/kg) or vehicle in the early afternoon daily for five days beginning on the day of surgery. All mice were habituated to a neutral object in their home cage for five days and underwent one 30-minute footshock/no shock training session during the illness period. After physiologic recovery (2 weeks), the mice underwent behavioral testing including open field exploration, object recognition testing in which they were presented with both the familiar (habituated) object and a novel object, and testing in the shock context. The results showed that drug treatment had no effect on behavior in the open field, including time spent in the center (VEH: 20.19±10.81 vs CORT: 22.32±12.87 sec; P=0.476). Drug treatment increased overall object exploration (12.28±10.79 vs 19.17±15.88 sec; P=0.049). Corticosterone-treated mice showed a preference for the familiar object (60.9±23.0% of total exploration time with familiar object; P=0.015), while vehicle-treated mice did not (54.1±23.3%; P=0.378). The increase in overall object exploration seen in corticosterone-treated mice could be accounted for by an increase in exploration of the familiar object. History of footshock increased freezing in the training context (3.96±2.54% vs 36.08±15.42%; P<0.0001) and corticosterone treatment had no effect (18.06±17.65% vs 22.16±21.19%; P=0.557). In conclusion, administration of corticosterone during infectious illness facilitated memory of a neutral object from the illness period, and recovered mice exhibited a preference for this object over a novel one. Corticosterone treatment had no impact on fear memory formed during illness. This is consistent with human literature suggesting that hydrocortisone decreases PTSD symptoms without impacting traumatic memories. These findings suggest that glucocorticoids selectively enhance the formation, consolidation, and/or recall of neutral but not fear memories during illness, which may rely on hippocampal circuitry. We further suggest that accurate memories of the illness period may influence patients’ perception of this experience and alter their risk for psychiatric sequelae.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Organic Disease or Psychosomatic Illness? A Re-Examination of the Royal Free Epidemic of 1955

Background and Objectives: Controversy exists over whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an organic disease or a psychosomatic illness. ME/CFS usually occurs as sporadic cases, but epidemics (outbreaks) have occurred worldwide. Myalgic encephalomyelitis was named to describe an outbreak affecting the lymphatic, muscular, and nervous systems that closed the Royal Free hospital for three months in 1955. Fifteen years later, two psychiatrists concluded that epidemic hysteria was the likely cause. ME/CFS research studies show multiple pathophysiological differences between patients and controls and a possible etiological role for infectious organisms, but the belief that ME/CFS is psychosomatic is widespread and has been specifically supported by the epidemic hysteria hypothesis for the Royal Free outbreak. Our objective was to obtain accounts from ex-Royal Free hospital staff who personally experienced the 1955 outbreak and evaluate evidence for it being an infectious illness versus epidemic hysteria. Materials and Methods: Statements in the newsletters of two organizations for staff who had worked at the Royal Free hospital invited anyone who had experienced the 1955 Royal Free outbreak to contact the authors. Accounts of the outbreak from telephone interviews and letters were evaluated against the “epidemic hysteria hypothesis” paper and original medical staff reports. Results: Twenty-seven ex-Royal Free hospital staff, including six who had developed ME, provided descriptions typical of an infectious illness affecting the lymphatic, muscular, and nervous systems, and were not consistent with epidemic hysteria. Conclusions: The 1955 Royal Free hospital epidemic of myalgic encephalomyelitis was an organic infectious disease, not psychogenic epidemic hysteria.

Core warming of coronavirus disease 2019 (COVID-19) patients undergoing mechanical ventilation—A protocol for a randomized controlled pilot study

Background Coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, is spreading rapidly across the globe, with little proven effective therapy. Fever is seen in most cases of COVID-19, at least at the initial stages of illness. Although fever is typically treated (with antipyretics or directly with ice or other mechanical means), increasing data suggest that fever is a protective adaptive response that facilitates recovery from infectious illness. Objective To describe a randomized controlled pilot study of core warming patients with COVID-19 undergoing mechanical ventilation. Methods This prospective single-site randomized controlled pilot study will enroll 20 patients undergoing mechanical ventilation for respiratory failure due to COVID-19. Patients will be randomized 1:1 to standard-of-care or to receive core warming via an esophageal heat exchanger commonly utilized in critical care and surgical patients. The primary outcome is patient viral load measured by lower respiratory tract sample. Secondary outcomes include severity of acute respiratory distress syndrome (as measured by PaO2/FiO2 ratio) 24, 48, and 72 hours after initiation of treatment, hospital and intensive care unit length of stay, duration of mechanical ventilation, and 30-day mortality. Results Resulting data will provide effect size estimates to guide a definitive multi-center randomized clinical trial. ClinicalTrials.gov registration number: NCT04426344. Conclusions With growing data to support clinical benefits of elevated temperature in infectious illness, this study will provide data to guide further understanding of the role of active temperature management in COVID-19 treatment and provide effect size estimates to power larger studies.