Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations.

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2, a novel coronavirus from the same family as SARS-CoV and Middle East respiratory syndrome coronavirus, has spread worldwide leading the World Health Organization to declare a pandemic. The disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID-19), presents flu-like symptoms which can become serious in high-risk individuals. Here, we provide an overview of the known clinical features and treatment options for COVID-19. We carried out a systematic literature search using the main online databases (PubMed, Google Scholar, MEDLINE, UpToDate, Embase and Web of Science) with the following keywords: 'COVID-19', '2019-nCoV', 'coronavirus' and 'SARS-CoV-2'. We included publications from 1 January 2019 to 3 April 2020 which focused on clinical features and treatments. We found that infection is transmitted from human to human and through contact with contaminated environmental surfaces. Hand hygiene is fundamental to prevent contamination. Wearing personal protective equipment is recommended in specific environments. The main symptoms of COVID-19 are fever, cough, fatigue, slight dyspnoea, sore throat, headache, conjunctivitis and gastrointestinal issues. Real-time PCR is used as a diagnostic tool using nasal swab, tracheal aspirate or bronchoalveolar lavage samples. Computed tomography findings are important for both diagnosis and follow-up. To date, there is no evidence of any effective treatment for COVID-19. The main therapies being used to treat the disease are antiviral drugs, chloroquine/hydroxychloroquine and respiratory therapy. In conclusion, although many therapies have been proposed, quarantine is the only intervention that appears to be effective in decreasing the contagion rate. Specifically designed randomized clinical trials are needed to determine the most appropriate evidence-based treatment modality.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/joim.13091

COVID-19 diagnosis and management: a comprehensive review.

A novel zoonotic coronavirus outbreak is spreading all over the world. This pandemic disease has now been defined as novel coronavirus disease 2019 (COVID-19), and is sustained by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the current gold standard for the etiological diagnosis of SARS-CoV-2 infection is (real time) reverse transcription polymerase chain reaction (rRT-PCR) on respiratory tract specimens, the diagnostic accuracy of this technique shall be considered a foremost prerequisite. Overall, potential RT-PCR vulnerabilities include general preanalytical issues such as identification problems, inadequate procedures for collection, handling, transport and storage of the swabs, collection of inappropriate or inadequate material (for quality or volume), presence of interfering substances, manual errors, as well as specific aspects such as sample contamination and testing patients receiving antiretroviral therapy. Some analytical problems may also contribute to jeopardize the diagnostic accuracy, including testing outside the diagnostic window, active viral recombination, use of inadequately validated assays, insufficient harmonization, instrument malfunctioning, along with other specific technical issues. Some practical indications can hence be identified for minimizing the risk of diagnostic errors, encompassing the improvement of diagnostic accuracy by combining clinical evidence with results of chest computed tomography (CT) and RT-PCR, interpretation of RT-PCR results according to epidemiologic, clinical and radiological factors, recollection and testing of upper (or lower) respiratory specimens in patients with negative RT-PCR test results and high suspicion or probability of infection, dissemination of clear instructions for specimen (especially swab) collection, management and storage, together with refinement of molecular target(s) and thorough compliance with analytical procedures, including quality assurance.

Potential preanalytical and analytical vulnerabilities in the laboratory diagnosis of coronavirus disease 2019 (COVID-19)

Background A false-negative case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is defined as a person with suspected infection and an initial negative result by reverse transcription-polymerase chain reaction (RT-PCR) test, with a positive result on a subsequent test. False-negative cases have important implications for isolation and risk of transmission of infected people and for the management of coronavirus disease 2019 (COVID-19). We aimed to review and critically appraise evidence about the rate of RT-PCR false-negatives at initial testing for COVID-19. Methods We searched MEDLINE, EMBASE, LILACS, as well as COVID-19 repositories, including the EPPI-Centre living systematic map of evidence about COVID-19 and the Coronavirus Open Access Project living evidence database. Two authors independently screened and selected studies according to the eligibility criteria and collected data from the included studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the proportion of false-negative test results using a multilevel mixed-effect logistic regression model. The certainty of the evidence about false-negative cases was rated using the GRADE approach for tests and strategies. All information in this article is current up to July 17, 2020. Results We included 34 studies enrolling 12,057 COVID-19 confirmed cases. All studies were affected by several risks of bias and applicability concerns. The pooled estimate of false-negative proportion was highly affected by unexplained heterogeneity (tau-squared = 1.39; 90% prediction interval from 0.02 to 0.54). The certainty of the evidence was judged as very low due to the risk of bias, indirectness, and inconsistency issues. Conclusions There is substantial and largely unexplained heterogeneity in the proportion of false-negative RT-PCR results. The collected evidence has several limitations, including risk of bias issues, high heterogeneity, and concerns about its applicability. Nonetheless, our findings reinforce the need for repeated testing in patients with suspicion of SARS-Cov-2 infection given that up to 54% of COVID-19 patients may have an initial false-negative RT-PCR (very low certainty of evidence). Systematic review registration Protocol available on the OSF website: https://tinyurl.com/vvbgqya.

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False-negative results of initial RT-PCR assays for COVID-19: A systematic review.

During the current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2), there has been an unprecedented level of global collaboration that has led to a rapid characterization of SARS–CoV-2 (1). Its sequence shares 79.6% identity to SARS–CoV (1, 2), the infectious virus that caused an epidemic in 2003 (2, 3). SARS–CoV-2 has a single-stranded, plus-sense, RNA genome of approximately 30 kb, which includes five major open reading frames encoding nonstructural replicase polyproteins and structural proteins (1), namely, spike (S) (4–6), envelope (E), membrane (M), and nucleocapsid (N) (7), and they are in the same order and of approximately the same sizes as those in SARS-CoV. The SARS–CoV-2 S protein is being used as the leading target antigen in vaccine development (8, 9). However, the complex molecular details of viral entry may lead to complications with the vaccine response, similar to those seen with HIV type 1 (HIV-1) Env protein vaccine efforts (10). The SARS–CoV-2 S gene has 76% amino acid similarity to the SARS-CoV S gene (11), and nonsynonymous mutations developed in the S protein as the SARS-CoV epidemic progressed (12, 13). In contrast, the N gene is more conserved and stable, with 90% amino acid homology and fewer mutations over time (2, 3, 11, 14–16). N proteins of many coronaviruses are highly immunogenic and are expressed abundantly during infection (17). High levels of IgG antibodies against N have been detected in sera from SARS patients (18), and the N protein is a representative antigen for the T-cell response in a vaccine setting, inducing SARS-specific T-cell proliferation and cytotoxic activity (19, 20). We have already shown that the middle or C-terminal region of the SARS-CoV N protein is important for eliciting antibodies against SARS-CoV during the immune response (21–23). New reports have additionally shown that the crystal structure of the SARS–CoV-2 nucleocapsid protein is similar to those of previously described coronavirus N proteins, but their surface electrostatic potential characteristics are distinct (7). Sheikh et al. studied the factors influencing N gene variations among 13 coronaviruses and how these affect virus-host relationships, reporting a high AT% and low GC% in the nucleotide contents of SARS coronavirus (24). In this issue, Cong et al. (17) used a mouse hepatitis virus (MHV) model to show that the viral nucleocapsid (N) protein contributes to forming helical ribonucleoproteins during the packaging of the RNA genome, regulating viral RNA synthesis during replication and transcription and modulating metabolism in infected subjects. This study complements others that have shown N to have multiple functions (25). It is becoming more evident just how critical this protein is for multiple steps of the viral life cycle. These reports offer important and timely insights relevant to the SARS–CoV-2 N protein, a vaccine target that has some distinct advantages over other potential SARS– CoV-2 antigens. Because of the conservation of the N protein sequence, the expanding Citation Dutta NK, Mazumdar K, Gordy JT. 2020. The nucleocapsid protein of SARS–CoV-2: a target for vaccine development. J Virol 94:e00647-20. https://doi.org/10.1128/JVI.00647-20. Editor Rebecca Ellis Dutch, University of Kentucky College of Medicine Copyright © 2020 American Society for Microbiology. All Rights Reserved. Address correspondence to Noton K. Dutta, ndutta1@jhmi.edu Published LETTER TO THE EDITOR

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The Nucleocapsid Protein of SARS-CoV-2: a Target for Vaccine Development.

Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.

Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review.

Background Singapore has completely banned e-cigarettes and the government’s cautious stance against vaping has been consistent. Despite this, vaping appears to have gained popularity in Singapore, especially among younger people. With the heavy marketing of vaping products on social media, it is possible that such marketing, due to its cross-border nature, is reaching younger Singaporeans and driving changes in vaping-related perceptions or behaviours. This study examines their exposure to vaping-related content on social media, and whether such exposure is associated with more positive perceptions of vaping or e-cigarette ever use. Methods Analysis of cross-sectional survey data of 550 adult (age 21–40 years) Singaporeans recruited via convenience methods in May 2022, using descriptive statistics, bivariate analyses, and multiple linear and logistic regression models. Results 16.9% of participants reported they had ever used e-cigarettes. 18.5% of those who used social media recalled seeing vaping-related content on a social media platform in the past 6 months, mostly from influencers or friends, and on Instagram, Facebook, TikTok and/or YouTube. Reporting exposure to such content was not associated with e-cigarette ever use. It was associated with having a more positive overall perception of vaping (β=1.47; 95% CI: 0.17 to 2.78), although no significant difference was observed when examining only health-related perceptions. Conclusion Even in a heavily regulated environment such as Singapore’s, people appear to be exposed to vaping-related content on social media platforms and this exposure is, in turn, associated with more positive perceptions of vaping, but not e-cigarette ever use.

Xian Yi Ng

Papers

Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review.

Vaping in a heavily regulated setting: cross-sectional survey of e-cigarette use, perceptions and social media exposure