Which vertebral level should be used to calculate sarcopenia in covid-19 patients? A systematic review and meta-analysis.

BACKGROUND & AIMS: Evidence shows that CT-derived sarcopenia can predict adverse outcomes in COVID-19 patients. However, discrepancies exist as to which vertebral level can be used to calculate sarcopenia which can effectively serve as a prognostic tool. Thus, we aim to investigate the difference in sarcopenia calculated at the Thoracic and Lumbar vertebral levels. METHODS: An online literature search was conducted on Electronic databases such as PubMed, Cochrane CENTRAL, and Google scholar. Meta-analysis was performed by using Revman 5.3 software. RESULTS: A total of 14 articles were selected for meta-analysis. The prevalence of sarcopenia calculated at the Thoracic level was 31% (95%CI 24%-37%; p < 0.00001; I2 = 86%), while sarcopenia calculated at the Lumbar vertebral level was 63% (95%CI 51%-75%; p < 0.00001; I2 = 88%). Meanwhile, sarcopenia calculated at the Upper thoracic level was a significant predictor of mortality OR 3.47 (95%CI 1.74-6.91; p = 0.0004; I2 = 56%)as compared to sarcopenia calculated at the lower thoracic OR 1.74 (95%Cl 0.91-3.33; p = 0.10; I2 = 60%)or lumbar level OR 2.49 (95%CI 0.45-13.72; p = 0.30; I2 = 57%). In addition to this sarcopenia calculated at the Upper thoracic level was also a significant predictor of severe illness OR 3.92 (95%CI 2.33-6.58; p < 0.00001; I2 = 0%) as compared to lower thoracic OR 1.40 (95%CI 0.78-2.53; p = 0.26; I2 = 67%) or lumbar level OR 1.64 (95%CI 0.26-10.50; p = 0.60; I2 = 81%) CONCLUSIONS: Sarcopenia calculated at the thoracic vertebrae and lumber level has different prognostic values. Sarcopenia is prevalent at the lumbar level. Sarcopenia at the thoracic level has a higher mortality and severity rate.

Air Leak Syndrome In Patients With Severe Covid Pneumonia.

Abstract: There are number of emerging studies that link the air leak syndrome (ALS) with COVID 19 disease but still data to explain the association, incidence and outcome in these patients is lacking. We aim to understand the risk factors and clinical outcome of these air leakage events in COVID 19 patients admitted to our institution. Methods: This is a single-centered case series conducted at the COVID unit of the SMBBIT in Karachi, Pakistan. Data collection was done from April 24, 2020 to June 10, 2021. Results: There were 19 patients with severe COVID pneumonia who developed air leaks. Most common finding was subcutaneous emphysema 94%. Four patients (21%) didn't receive positive pressure ventilation in any form. Median time of developing air leak from admission is 5 [2-9] and from PPV is 2 [1-3] days. There was high percentage of mortality 84.5 % in these patients.

Nirmatrelvir exerts distinct antiviral potency against different human coronaviruses.

Nirmatrelvir is the main component of Paxlovid, an oral antiviral drug approved for the treatment of COVID-19 caused by SARS-COV-2 infection. Nirmatrelvir targets the main protease (Mpro), which is substantially conserved among different coronaviruses. Here, our molecular docking analysis indicates comparable affinity of nirmatrelvir binding to the Mpro enzymes of SARS-CoV-2 and three seasonal coronaviruses (OC43, 229E and NL63). However, in cell culture models, we found that nirmatrelvir potently inhibited SARS-CoV-2, OC43 and 229E, but not NL63. The insensitivity of NL63 to nirmatrelvir treatment was demonstrated at both viral replication and infectious titer levels. The antiviral activity of nirmatrelvir against OC43 and 229E was further confirmed in human airway organoids. The combination of nirmatrelvir and molnupiravir exerted differential patterns of antiviral response against OC43 and 229E. These results revealed disparities in the ability of nirmatrelvir to inhibit different coronaviruses, and caution against repurposing of nirmatrelvir as a pan-coronavirus treatment.

In silico analysis reveals hypoxia-induced miR-210-3p specifically targets SARS-CoV-2 RNA.

Human coronaviruses (HCoVs) until the emergence of SARS in 2003 were associated with mild cold and upper respiratory tract infections. The ongoing pandemic caused by SARS-CoV-2 has enhanced the potential for infection and transmission as compared to other known members of this family. MicroRNAs (miRNA) are 21-25 nucleotides long non-coding RNA that bind to 3' UTR of genes and regulate almost every aspect of cellular function. Several human miRNAs have been known to target viral genomes, mostly to downregulate their expression and sometimes to upregulate also. In some cases, host miRNAs could be sequestered by the viral genome to create a condition for favourable virus existence. The ongoing SARS CoV-2 pandemic is unique based on its transmissibility and severity and we hypothesised that there could be a unique mechanism for its pathogenesis. In this study, we exploited in silico approach to identify human respiratory system-specific miRNAs targeting the viral genome of three highly pathogenic HCoVs (SARS-CoV-2 Wuhan strain, SARS-CoV, and MERS-CoV) and three low pathogenic HCoVs (OC43, NL63, and HKU1). We identified ten common microRNAs that target all HCoVs studied here. In addition, we identified unique miRNAs which targeted specifically one particular HCoV. miR-210-3p was the single unique lung-specific miRNA, which was found to target the NSP3, NSP4, and NSP13 genes of SARS-CoV-2. Further miR-210-NSP3, miR-210-NSP4, and miR-210-NSP13 SARS-CoV-2 duplexes were docked with the hAGO2 protein (PDB ID 4F3T) which showed Z-score values of -1.9, -1.7, and -1.6, respectively. The role of miR-210-3p as master hypoxia regulator and inflammation regulation may be important for SARS-CoV-2 pathogenesis. Overall, this analysis advocates that miR-210-3p be investigated experimentally in SARS-CoV-2 infection.Communicated by Ramaswamy H. Sarma.

The Anticipated Future of Public Health Services Post COVID-19: Viewpoint.

In March 2020, the World Health Organization declared COVID-19 as a global pandemic. The COVID-19 pandemic has affected various public health functions and essential services in different ways and magnitudes. Although all countries have witnessed the effect of COVID-19, the impact differed based on many factors including the integrity and resiliency of the countries' health systems. This paper presents opinions and expectations of the authors about the anticipated changes in the future of public health at the global, regional, and national levels. The viewpoint is based on the current efforts and challenges that various stakeholders have carried out to control COVID-19 and the contribution from the literature on the future of public health. Numerous agencies and actors are involved in the fight against COVID-19 with variations in their effectiveness. The public health services showed weaknesses in most of the countries, in addition to the lack of adequate curative medicine settings. The pandemic highlighted the need for better governance and stronger and more resilient health systems and capacities. The COVID-19 experience has also emphasized the importance of coordination and collaboration among the countries and stakeholders. The COVID-19 pandemic might lead to a wide discussion to improve international and national approaches to prepare for and respond to similar events in terms of preparedness and response mechanisms and tools. Public health will not be the same as before COVID-19. New health priorities, approaches, and new agendas will be on the table of the global platforms and initiatives. More investment in research and technology to meet the demand for new vaccines and medicines, innovative methods like distance learning and working, more respect and remuneration to health professionals, and normalization of the public health and social measures that were induced during the COVID-19 pandemic are expected to be seen in future.

Structural analysis of spike proteins from SARS-CoV-2 variants of concern highlighting their functional alterations.

Aim: Mutations in the SARS-CoV-2 spike (S) protein have dramatically changed the transmissibility and pathogenicity of the virus. Therefore, we studied the binding affinity of Omicron spike-receptor binding domain (S-RBD) with human ACE2 receptor. Materials & methods: We used pyDockWEB and HADDOCK 2.4 docking for our study. Results: Computational docking indicated higher binding affinity of Omicron S-RBD as compared with wild-type SARS-CoV-2 and Delta S-RBD with ACE2. Interface analysis suggested four mutated residues of Omicron S-RBD for its enhanced binding. We also showed decreased binding affinity of Omicron and Delta S-RBDs with monoclonal antibodies. Conclusion: Compared with wild-type SARS-CoV-2, Omicron S-RBD exhibit higher binding with ACE2 and lower affinity against monoclonal antibodies.

Structural analysis of spike proteins from SARS-CoV-2 variants of concern highlighting their functional alterations

Aim: Mutations in the SARS-CoV-2 spike (S) protein have dramatically changed the transmissibility and pathogenicity of the virus. Therefore, we studied the binding affinity of Omicron spike-receptor binding domain (S-RBD) with human ACE2 receptor. Materials & methods: We used pyDockWEB and HADDOCK 2.4 docking for our study. Results: Computational docking indicated higher binding affinity of Omicron S-RBD as compared with wild-type SARS-CoV-2 and Delta S-RBD with ACE2. Interface analysis suggested four mutated residues of Omicron S-RBD for its enhanced binding. We also showed decreased binding affinity of Omicron and Delta S-RBDs with monoclonal antibodies. Conclusion: Compared with wild-type SARS-CoV-2, Omicron S-RBD exhibit higher binding with ACE2 and lower affinity against monoclonal antibodies.

Epigallocatechin gallate (EGCG) attenuates severe acute respiratory coronavirus disease 2 (SARS-CoV-2) infection by blocking the interaction of SARS-CoV-2 spike protein receptor-binding domain to human angiotensin-converting enzyme 2.

The outbreak of the coronavirus disease 2019 caused by the severe acute respiratory syndrome coronavirus 2 triggered a global pandemic where control is needed through therapeutic and preventive interventions. This study aims to identify natural compounds that could affect the fusion between the viral membrane (receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 spike protein) and the human cell receptor angiotensin-converting enzyme 2. Accordingly, we performed the enzyme-linked immunosorbent assay-based screening of 10 phytochemicals that already showed numerous positive effects on human health in several epidemiological studies and clinical trials. Among these phytochemicals, epigallocatechin gallate, a polyphenol and a major component of green tea, could effectively inhibit the interaction between the receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 spike protein and the human cell receptor angiotensin-converting enzyme 2. Alternately, in silico molecular docking studies of epigallocatechin gallate and angiotensin-converting enzyme 2 indicated a binding score of -7.8 kcal/mol and identified a hydrogen bond between R393 and angiotensin-converting enzyme 2, which is considered as a key interacting residue involved in binding with the severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain, suggesting the possible blocking of interaction between receptor-binding domain and angiotensin-converting enzyme 2. Furthermore, epigallocatechin gallate could attenuate severe acute respiratory syndrome coronavirus 2 infection and replication in Caco-2 cells. These results shed insight into identification and validation of severe acute respiratory syndrome coronavirus 2 entry inhibitors.

Opportunistic Infections in COVID-19: A Systematic Review and Meta-Analysis

The prevalence, incidence, and characteristics of bacterial infections in patients infected with severe acute respiratory syndrome coronavirus 2 are not well understood and have been raised as an important knowledge gap. Therefore, our study focused on the most common opportunistic infections/secondary infections/superinfections in coronavirus disease 2019 (COVID-19) patients.This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Eligible studies were identified using PubMed/Medline since inception to June 25, 2021. Studies meeting the inclusion criteria were selected. Statistical analysis was conducted in Review Manager 5.4.1. A random-effect model was used when heterogeneity was seen to pool the studies, and the result was reported as inverse variance and the corresponding 95% confidence interval.We screened 701 articles comprising 22 cohort studies which were included for analysis. The pooled prevalence of opportunistic infections/secondary infections/superinfections was 16% in COVID-19 patients. The highest prevalence of secondary infections was observed among viruses at 33%, followed by bacteria at 16%, fungi at 6%, and 25% among the miscellaneous group/wrong outcome.Opportunistic infections are more prevalent in critically ill patients. The isolated pathogens included Epstein-Barr virus, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Hemophilus influenza, and invasive pulmonary aspergillosis. Large-scale studies are required to better identify opportunistic/secondary/superinfections in COVID-19 patients.

Association between Sleep Quality and Mental Health among Patients at a Post-COVID-19 Recovery Clinic.

A growing body of research documents the persistence of physical and neuropsychiatric symptoms following the resolution of acute COVID-19 infection. To the best of our knowledge, no published study has examined the interaction between insomnia and mental health. Accordingly, we proposed to examine new diagnoses of insomnia, and referrals to pulmonary and sleep medicine clinics for treatment of sleep disorders, in patients presenting to one post-acute COVID-19 recovery clinic. Additionally, we aimed to examine the relationship between poor sleep quality, depression, anxiety, and post-traumatic stress. Patients presented to the clinic on average 2 months following COVID-19 infection; 51.9% (n = 41) were hospitalized, 11.4% (n = 9) were in the intensive care unit, 2.5% (n = 2) were on a mechanical ventilator, and 38.0% (n = 30) were discharged on oxygen. The most commonly reported symptom was fatigue (88%, n = 70), with worse sleep following a COVID-19 infection reported in 50.6% (n = 40). The mean PSQI score was 9.7 (82.3%, n = 65 with poor sleep quality). The mean GAD-7 score was 8.3 (22.8%, n = 14 with severe depression). The mean PHQ-9 was 10.1 (17.8%, n = 18 with severe anxiety). The mean IES-6 was 2.1 (54.4%, n = 43 with post-traumatic stress). Poor sleep quality was significantly associated with increased severity of depression, anxiety, and post-traumatic stress. Future work should follow patients longitudinally to examine if sleep, fatigue, and mental health symptoms improve over time.

Analysis of Learner’s Sentiments to Evaluate Sustainability of Online Education System during COVID-19 Pandemic

Education is an important domain that may be improved by analyzing the sentiments of learners and educators. Evaluating the sustainability of the education system is critical for the continuous improvement and satisfaction of the learner’s community. This research work focused on the evaluation of the effectiveness of the online education system that has been adopted during the COVID-19 pandemic. For this purpose, sentiments/reviews of learners were collected from the Twitter website regarding the education domain during COVID-19. To automate the process of evaluation, a hybrid approach was applied that used a knowledgebase of opinion words along with machine learning and boosting algorithms with n-grams (unigram, bigram, trigram and combination of all these n-grams). This automated approach helped to evaluate the transition of the education system in different circumstances. An ensemble classifier was created in combination with a customized knowledgebase using classifiers that individually performed best with each of the n-grams. Due to the imbalanced nature of the data (tweets), these operations were performed by applying the synthetic minority oversampling technique (SMOTE). The obtained results show that the use of a customized knowledgebase not only improved the performance of the individual classifiers but also produced quality results with the ensemble model. As per the observed results, the online education system was not found sustainable as the majority of the learners were badly affected due to some important aspects (health issues, lack of training and resources).

Repurposing dyphylline as a pan-coronavirus antiviral therapy.

Background: In the last two decades, the world has witnessed the emergence of zoonotic corona viruses (CoVs), which cause mild to severe respiratory diseases in humans. Human coronaviruses (HCoVs), mainly from the alpha-CoV and beta-CoV genera, have evolved to be highly pathogenic, such as SARS-CoV-2 causing the COVID-19 pandemic. These coronaviruses carry functional enzymes necessary for the virus life cycle, which represent attractive antiviral targets. Methods & Results: We aimed to therapeutically target the main protease (Mpro) of HCoV-NL63 and HCoV-229E (from alpha-CoV genus) and HCoV-OC43 and SARS-CoV-2 (from beta-CoV genus). Through virtual screening, we identified an FDA-approved drug dyphylline, a xanthine derivate, that binds to the catalytic dyad residues; histidine and cystine of the Mpro structures. Importantly, dyphylline dose-dependently inhibited the viral replication in cell culture models infected with the viruses. Conclusion: Our findings support the repurposing of dyphylline as a pan-coronavirus antiviral agent.

Alterations in Clinical Characteristics of Blood Donors Post COVID-19 Recovery.

BACKGROUND: Corona Virus Disease-19 (COVID-19), a current worldwide pandemic is the cause of serious concern. Risk-adjusted differences in outcomes of the patients are not well characterized. Therefore, susceptibility to infection with respect to blood group, blood pressure, pulse rate, hemoglobin, age, and BMI is analyzed in this study. METHODS: Blood donors of all ages and gender, who recovered from COVID-19 infection, were selected for the study. Samples were collected from the regional laboratory and the central blood bank of Hafr al Batin, Saudi Arabia. Out of 1508 healthy blood donors, 134 had recovered from corona without any preexisting diseases. RESULTS: Major donors were male (85.1%). 28% of donors were in the age range of 26-35 years. O+(32.8%) donors were in majority. Systolic and diastolic blood pressure and pulse rate elevated significantly in the age group 46-55 (p<0.05) and 56-65 (p<0.001). Systolic blood pressure in males (134.13 ± 9.57) was significantly higher (p<0.05) than in females (129.35 ± 10.61). Donors with Rh+ had significantly higher systolic (p<0.05) and pulse rate (p<0.05) as compared to Rh-. DISCUSSION: O+ donors were found to be highly susceptible. Blood pressure, pulse rate and Hb altered with age. Males exhibited higher variation in systolic blood pressure, with the Rh+ factor playing a predominant role. Donors above 45-years of age and with a high BMI had significantly elevated blood pressure and pulse. These results are challenging or contradictory to the results of Turkish and Chinese studies where blood group A+ was more predominantly affected by the SARS-CoV-2 with the minimum infection rate in females and Rh- donors. CONCLUSION: Factors like blood group, age, physical characteristics and BMI should be taken into account before initiating any therapeutic approach to obtain the best possible outcomes with minimum adverse effects from the current drugs utilized for SARS CoV-2 treatment, especially with the age group of 45 years and above.

The COVID-19 Pandemic and Overconfidence Bias: The Case of Cyclical and Defensive Sectors

This research paper analyses the impact of COVID-19 to investigate the overconfidence bias in 12 cyclical and defensive sectors in pre- and during COVID-19 periods using daily data from 1 January 2015 to 31 December 2020. The results of VAR show that in the pre COVID-19 phase overconfidence bias is more prevalent in all the cyclical sectors;in particular, MEDIA, METAL and REALTY have highly significant coefficients . In the defensive sectors, the VAR outcomes are not as strong as we expected, except for SERVICES. During the COVID-19 period, the investor shifted their focus to COVID-19-related opportunities, leading to a surge in the IT and PHARMA sectors. In both phases, METAL, MEDIA and REALTY exhibit overconfidence-driven stock trading behaviour. ENERGY is the only sector in both the phases that does not witness overconfidence bias.

A qualitative insight into the perceptions and COVID-19 vaccine hesitancy among Pakistani pharmacists.

A qualitative exploration of pharmacists' perceptions regarding COVID-19 conspiracies and their willingness to get vaccinated. A semi-structured questionnaire guide was developed using ground theory to conduct in-depth interviews. A total of 36 participants gave consent for an audio-recorded interview. Results have shown that most of the respondents believed that SARS-CoV-2 is a natural virus, not man-made, that causes a disease just like other viruses and it is absurd to believe that the vaccine is being used by foreign powers for the implantation of microchips just to control humans. A general opinion thatwhich reflected from the in-depth interview is that the pharmaceutical companies may be hiding some important information on COVID-19 to promote the sale of their product. Some doubts on the reliability and trustworthiness on the COVID-19 vaccine safety and efficacy data were noticed among the respondents. Factors leading to COVID-19 vaccine hesitancy were adverse reaction, cost of COVID-19 vaccine, and limited data on safety and efficacy profile of COVID-19 vaccine. COVID-19 vaccine hesitancy among health professionals is a major hindrance to our current fight against COVID-19 pandemic. Findings of this study are alarming, and the stakeholders must consider this ongoing vaccination campaign as an opportunity to formulate a mechanism to ensure high vaccination rate among general public and healthcare providers in Pakistan.KEY POINTSWhat was already known?According to World Health Organization (WHO), vaccine hesitancy is one of the ten major threats to global healthcare system and it is a major barrier to achieve herd immunity around the globe.Pakistan has begun vaccinating its people in a systematic phase-wise manner under which the healthcare workers and elderly people are prioritized for vaccination.Previous experience tells us that vaccine hesitancy is a major problem in Pakistan and it is better to understand perceptions of pharmacists about COVID-19 vaccine who are the primary source of information for most of general population.What this study adds:This study is first of its kind to explore vaccine hesitancy among Pakistani pharmacists and the results of this study show that majority of the participants were willing to get COVID-19 vaccine and few of them have even got themselves vaccinated at the start of vaccination campaign.Many among the willing participants considered cost of vaccine, adverse reactions, limited data, safety, and efficacy as major hindrance to their decision to get vaccine.Few participants were found highly vaccine-hesitant because of their staunch belief in the prevalent myths and rumors about COVID-19 vaccine.

Differing pan-coronavirus antiviral potency of boceprevir and GC376 in vitro despite discordant molecular docking predictions.

Given the structural similarities of the viral enzymes of different coronaviruses (CoVs), we investigated the potency of the anti-SARS-CoV-2 agents boceprevir and GC376 for counteracting seasonal coronavirus infections. In contrast to previous findings that both boceprevir and GC376 are potent inhibitors of the main protease (Mpro) of SARS-CoV-2, we found that GC376 is much more effective than boceprevir in inhibiting SARS-CoV-2 and three seasonal CoVs (NL63, 229E, and OC43) in cell culture models. However, these results are discordant with a molecular docking analysis that suggested comparable affinity of boceprevir and GC376 for the different Mpro enzymes of the four CoVs. Collectively, our results support future development of GC376 but not boceprevir (although it is an FDA-approved antiviral medication) as a pan-coronavirus antiviral agent. Furthermore, we caution against overinterpretation of in silico data when developing antiviral therapies.

Serum albumin levels monitoring in ICU in early days and mortality risk association in patients with moderate to severe COVID-19 pneumonia.

Objective: To establish correlation between serum albumin during early days of ICU admission and risk of death in COVID-19 pneumonia. Methods: In this retrospective study, we included 76 patients hospitalized in ICU, who stayed for at least four days with COVID-19 pneumonia, from May 1, 2020 to June 30, 2020 in Lahore Health Care Hospital and Al-Shafi Hospital. Patients were labelled as COVID-19 pneumonia on radiological basis as bilateral 'ground-glass opacity' in lower zones and RT-PCR positive result in nasopharyngeal swab. All patients were oxygen dependent, either on high flow oxygen via non rebreathing mask or invasive positive pressure ventilation support. Serum albumin levels were measured daily from first day to fourth day of ICU admission. The data was analyzed using SPSS version 26 and Microsoft excel 2016. Results: Out of 76 patients of COVID-19 pneumonia admitted in ICU who stayed for more than four days, 38 patients expired. The mean age of all the patients was 58.9±12.56 years, 38(50%) of the patients were ≥60 years and 49 (62%) of them were male. On day four of ICU admission, mean serum albumin of discharged patients was 3.83±0.22 g/dl while mean serum albumin level of expired patients was 2.96±0.46 g/dl. Strong negative correlation (r = -767) was found between decrease in serum albumin level and increase number of deaths from COVID-19 pneumonia. Weak correlation was observed between increase in serum CRP and increase number of deaths in the same patients. Conclusion: Daily monitoring of serum albumin level of COVID-19 pneumonia patients can be used as a biological marker for monitoring of cytokine storm and risk of death in COVID-19 pneumonia.

Dual targeting of 3CLpro and PLpro of SARS-CoV-2: A novel structure-based design approach to treat COVID-19.

With the rapid growth of the COVID-19 (coronavirus disease 2019) pandemic across the globe, therapeutic attention must be directed to fight the novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). However, developing new antiviral drugs and vaccines is time-consuming, so one of the best solutions to tackle this virus at present is to repurpose ready-to-use drugs. This paper proposes the repurposing of the Food and Drug Administration (FDA)-approved, purchasable, and naturally occurring drugs for preventive and therapeutic use. We propose to design a dual-inhibitor for the SARS-CoV-2 cysteine proteases-3 Chemotrypsin-like protease or main protease (3CLpro or Mpro) and Papain-like protease (PLpro) responsible for processing the translated polyprotein chain from the viral RNA yielding functional viral proteins. For virtual screening, an unbiased blind docking was performed from which the top nine dual-targeting inhibitors for 3CLpro and PLpro were selected. The nine repurposed drugs, block the catalytic dyad (His41 and Cys145) of 3CLpro as well as the catalytic triad (Cys111, His272, and Asp286) of PLpro. Repurposing known drugs will not only pave the way for rapid in-vitro and in-vivo studies to battle the SARS-CoV-2 but will also expedite the quest for a potent anti-coronaviral drug.