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1.
The Lancet. Infectious diseases ; 2022.
Article in English | EuropePMC | ID: covidwho-1837602

ABSTRACT

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19. Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 μg in 0·30 mL;full dose) or mRNA-1273 (Moderna;50 μg in 0·25 mL;half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (anti-spike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing. Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group). Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose. Funding UK Vaccine Task Force and National Institute for Health Research.

2.
J Infect ; 2022 Apr 09.
Article in English | MEDLINE | ID: covidwho-1778315

ABSTRACT

OBJECTIVES: To evaluate the persistence of immunogenicity three months after third dose boosters. METHODS: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study. RESULTS: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30-94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461-10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 µg) or BNT (30 µg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 µg) versus BNT (30 µg) ranging between 0.74-0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses. CONCLUSIONS: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.

3.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-332455

ABSTRACT

Background: Many high-income countries have deployed third “booster” doses of COVID-19 vaccines to populations and some countries have started offering fourth doses. Methods: The COV-BOOST trial is a multicentre, randomised, controlled, phase II trial of seven COVID-19 vaccines as third dose boosters. The current study invited participants who received BNT162b2 (BNT) as third dose in COV-BOOST to be randomised to receive a fourth dose of BNT or mRNA1273 (50 µg, half-m1273). The COV-BOOST trial is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. Results: Between 11 and 25 January 2022, 166 participants in the original BNT arm were randomised and received a fourth dose vaccine. The median age was 70.1 (interquartile range: 51.6-77.5) years with 51.8 % (n=86) female participants. The median interval between third and fourth dose was 208.5 (interquartile range: 203.25-214.75) days.Pain and fatigue were the most common local and systemic solicited adverse events for BNT and half-m1273. None of three serious adverse events reported after a fourth dose were related to study vaccine.The fold rises in anti-spike IgG pre- and post-fourth dose were 12.19 (95%CI: 10.37-14.32) and 15.90 (95%CI: 12.92-19.58) in BNT and half-m1273 arms respectively, with fold changes compared to the post third dose-peak of 1.59 (95%CI: 1.41-1.78) and 2.19 (95%CI: 1.90-2.52). T cell responses also boosted. Conclusions: Fourth dose COVID-19 mRNA booster vaccines are well-tolerated and boost cellular and humoral immunity up to, and beyond peak levels achieved following third dose boosters (ISRCTN: 73765130).

4.
Lancet ; 398(10318): 2258-2276, 2021 12 18.
Article in English | MEDLINE | ID: covidwho-1550152

ABSTRACT

BACKGROUND: Few data exist on the comparative safety and immunogenicity of different COVID-19 vaccines given as a third (booster) dose. To generate data to optimise selection of booster vaccines, we investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT). METHODS: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19. Participants were aged older than 30 years, and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course, with no history of laboratory-confirmed SARS-CoV-2 infection. 18 sites were split into three groups (A, B, and C). Within each site group (A, B, or C), participants were randomly assigned to an experimental vaccine or control. Group A received NVX-CoV2373 (Novavax; hereafter referred to as NVX), a half dose of NVX, ChAd, or quadrivalent meningococcal conjugate vaccine (MenACWY)control (1:1:1:1). Group B received BNT, VLA2001 (Valneva; hereafter referred to as VLA), a half dose of VLA, Ad26.COV2.S (Janssen; hereafter referred to as Ad26) or MenACWY (1:1:1:1:1). Group C received mRNA1273 (Moderna; hereafter referred to as m1273), CVnCov (CureVac; hereafter referred to as CVn), a half dose of BNT, or MenACWY (1:1:1:1). Participants and all investigatory staff were blinded to treatment allocation. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population. Secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ISRCTN, number 73765130. FINDINGS: Between June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control. The median ages of ChAd/ChAd-primed participants were 53 years (IQR 44-61) in the younger age group and 76 years (73-78) in the older age group. In the BNT/BNT-primed participants, the median ages were 51 years (41-59) in the younger age group and 78 years (75-82) in the older age group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were White, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were White. Three vaccines showed overall increased reactogenicity: m1273 after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 after BNT/BNT. For ChAd/ChAd-primed individuals, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 (99% CI 1·5-2·3) in the half VLA group to 32·3 (24·8-42·0) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·1 (95% CI 0·7-1·6) for ChAd to 3·6 (2·4-5·5) for m1273. For BNT/BNT-primed individuals, spike IgG GMRs ranged from 1·3 (99% CI 1·0-1·5) in the half VLA group to 11·5 (9·4-14·1) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·0 (95% CI 0·7-1·6) for half VLA to 4·7 (3·1-7·1) for m1273. The results were similar between those aged 30-69 years and those aged 70 years and older. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30-69 years than those aged 70 years or older. Serious adverse events were uncommon, similar in active vaccine and control groups. In total, there were 24 serious adverse events: five in the control group (two in control group A, three in control group B, and zero in control group C), two in Ad26, five in VLA, one in VLA-half, one in BNT, two in BNT-half, two in ChAd, one in CVn, two in NVX, two in NVX-half, and one in m1273. INTERPRETATION: All study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination. FUNDING: UK Vaccine Taskforce and National Institute for Health Research.


Subject(s)
/administration & dosage , COVID-19/prevention & control , Immunization, Secondary/methods , Immunogenicity, Vaccine , Adult , Aged , Aged, 80 and over , COVID-19/immunology , Female , Humans , Male , Middle Aged , Pandemics , Patient Safety , SARS-CoV-2 , United Kingdom
5.
Membranes (Basel) ; 11(11)2021 Nov 11.
Article in English | MEDLINE | ID: covidwho-1534180

ABSTRACT

In this study, granulated activated charcoal (GAC) and bio charcoal (BC) is used as a filler in P3 biosand bag filter to study their filtration performance against a range of fluoride impurities from 1-1400 mg/L. A set of experiments are done to analyze the filtration efficiency of the sandbag filter against fluoride impurities after incorporating different amounts (e.g., 0.2, 2 kg) and a combination of GAC and BC. A combination of filler GAC and BC (1 kg each) have exhibited excellent results with 100% fluoride removal efficiency against 5 mg/L fluoride impurities for an entire experimental time of 165 min. It is because of the synergetic effect of adsorption caused by the high surface area (739 m2/g) of GAC and hydroxyapatite groups in BC. The data from remediation experiments using individual GAC and BC are fitted into the Langmuir and Freundlich Isotherm Models to check their adsorption mechanism and determine GAC and BC's maximum adsorption capacity (Qm). The remediation data for both GAC and BC have shown the better fitting to the Langmuir Isotherm Model with a high R2 value of 0.994 and 0.970, respectively, showing the excellent conformity with monolayer adsorption. While the GAC and BC have presented negative Kf values of -1.08 and -0.72, respectively, for Freundlich Model, showing the non-conformity to multilayer adsorption. The Qm values obtained from Langmuir Model for GAC is 6.23 mg/g, and for BC, it is 9.13 mg/g. The pH study on adsorption efficiency of individual GAC and BC against 5 mg/L of fluoride impurities indicates the decrease in removal efficiency with an increase in pH from 3 to 9. For example, BC has shown removal efficiency of 99.8% at pH 3 and 99.5% at pH 9, while GAC has exhibited removal efficiency of 96.1% at pH 3 and 95.9% at pH 9. Importantly, this study presents the significance of the synergetic application of GAC and BC in the filters, where GAC and BC are different in their origin, functionalities, and surface characteristics.

6.
Applied Sciences ; 11(21):10478, 2021.
Article in English | MDPI | ID: covidwho-1512082

ABSTRACT

Xenobiotic Triclosan (TCS) is of great concern because of its existence in a variety of personal, household and healthcare products and continuous discharge in water worldwide. Excessive use of TCS-containing sanitizers and antiseptic products during the COVID-19 pandemic further increased its content in aquatic ecosystems. The present study deals with the cyto-genotoxic effects and biochemical alterations in the hatchlings of Labeo rohita on exposure to environmentally relevant concentrations of TCS. Three-days-old hatchlings were exposed to tap water, acetone (solvent control) and 4 environmentally relevant concentrations (6.3, 12.6, 25.2 and 60 µg/L) of TCS for 14 days and kept for a recovery period of 10 days. The significant concentration-dependent decline in cell viability but increase in micronucleated cells, nucleo-cellular abnormalities (NCAs) and DNA damage parameters like tail length, tail moment, olive tail moment and percent of tail DNA after exposure persisted till the end of recovery period. Glucose, triglycerides, cholesterol, total protein, albumin, total bilirubin, uric acid and urea (except for an increase at 60 µg/L) showed significant (p ≤ 0.05) concentration-dependent decrease after 14 days of exposure. The same trend (except for triglycerides, albumin and total bilirubin) continued till 10 days post exposure. In comparison to control, transaminases (alanine and aspartate aminotransferases) increased (p ≤ 0.05) after exposure as well as the recovery period, while a decline in alkaline phosphatase after exposure was followed by a significant increase during the recovery period. The results show that the environmentally relevant concentrations of TCS cause deleterious effects on the hatchlings of L. rohita.

7.
Crit Care Explor ; 3(10): e547, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1470172

ABSTRACT

To assess 30-day mortality in coronavirus disease 2019 acute respiratory distress syndrome patients transferred from rural Appalachian hospitals. DESIGN: Retrospective case controlled, based on consecutive patients transferred and admitted from rural hospitals to a tertiary-care ICU. The primary outcome was all-cause 30-day mortality. Kaplan-Meier method and log-rank test were used in the survival data analysis. SETTING: Medical ICU, West Virginia University Hospital, Morgantown, WV. PATIENTS: All adult patients admitted to the ICU for coronavirus disease 2019 disease between September 30, 2020, and December 2, 2020. INTERVENTION: Not applicable. MEASUREMENTS AND MAIN RESULTS: Seventy-nine consecutive coronavirus disease 2019 patients were admitted to the ICU during the defined period. Overall mortality of the cohort was 54%. Of the 79 patients, 50 were transferred from critical access hospitals/rural facilities with coronavirus disease 2019-induced acute respiratory distress syndrome. A control group consisted of 39 patients admitted to the ICU with noncoronavirus disease 2019 acute respiratory distress syndrome who were intubated and mechanically ventilated. Thirty-day mortality in patients with coronavirus disease 2019 admitted to the ICU was significantly higher than the control group (68% vs 42%) (p = 0.034). Mean Sequential Organ Failure Assessment scores were similar in both coronavirus disease 2019 acute respiratory distress syndrome group and controls. Intubation in patients 70 years or older and mechanical ventilation for over 5 days was associated with significantly higher mortality. CONCLUSIONS: Our data on critically ill and mechanically ventilated coronavirus disease 2019 acute respiratory distress syndrome patients transferred from critical access hospitals/rural facilities have increased mortality compared with noncoronavirus disease 2019 acute respiratory distress syndrome controls. These data suggest that lack or delay in access to tertiary care may impact coronavirus disease 2019 outcome in rural areas. Intubated patients 70 years old or more and mechanical ventilation for over 5 days may be a risk factor for increased mortality. These data may help physicians and hospital administrators in rural areas for optimal utilization of limited resources.

8.
Int J Infect Dis ; 111: 281-287, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1371471

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of pegylated interferon alpha-2b (PEG IFN-α2b) administered in conjunction with the standard of care (SOC) in subjects with moderate coronavirus disease-19 (COVID-19). METHODS: In this study, adult subjects with confirmed moderate COVID-19 were randomized in a 1:1 ratio to receive either PEG IFN-α2b + SOC or SOC alone. The primary endpoint was a two-point improvement in clinical status on Day 11, measured by the World Health Organization's seven-point ordinal scale. RESULTS: Of 250 subjects, 120 were randomized to the PEG IFN-α2b + SOC arm and 130 were randomized to the SOC arm. The results for the PEG IFN + SOC arms vs the SOC arm for the proportion of subjects with a two-point improvement in the seven-point ordinal scale were 80.36% vs 68.18% (P=0.037) on Day 8, 91.60% vs 92.56% (P=0.781) on Day 11, and 94.12% vs 95.93% (P=0.515) on Day 15. There was a time-dependent decrease in the biomarkers in both arms, and no clinically significant changes in laboratory parameters. The safety profile was similar in both arms. CONCLUSION: PEG IFN-α2b induced early viral clearance, improved the clinical status, and decreased the duration of supplemental oxygen. It provides a viable treatment option and can limit the spread of severe acute respiratory syndrome coronavirus-2.


Subject(s)
COVID-19 , Adult , Antiviral Agents/adverse effects , Humans , Interferon alpha-2 , Interferon-alpha/adverse effects , Polyethylene Glycols/adverse effects , Recombinant Proteins , SARS-CoV-2 , Treatment Outcome
9.
Results Phys ; 30: 104630, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1336891

ABSTRACT

This article discusses short term forecasting of the Novel Corona Virus (COVID -19) data for infected, recovered and active cases using the Machine learned hybrid Gaussian and ARIMA method for the spread in India. The Covid-19 data is obtained from the World meter and MOH (Ministry of Health, India). The data is analyzed for the period from January 30, 2020 (the first case reported) to October 15, 2020. Using ARIMA (2, 1, 0), we obtain the short forecast up to October 31, 2020. The several statistics parameters have tested for the goodness of fit to evaluate the forecasting methods but the results show that ARIMA (2, 1, 0) gives better forecast for the data system. It is observed that COVID 19 data follows quadratic behavior and in long run it spreads with high peak roughly estimated in September 18, 2020. Also, using nonlinear regression it is observed that the trend in long run follows the Gaussian mixture model. It is concluded that COVID 19 will follow secondary shock wave in the month of November 2020. In India we are approaching towards herd immunity. Also, it is observed that the impact of pandemic will be about 441 to 465 days and the pandemic will end in between April-May 2021. It is concluded that primary peak observed in September 2020 and the secondary shock wave to be around November 2020 with sharp peak. Thus, it is concluded that the people should follow precautionary measures and it is better to maintain social distancing with all safety measures as the pandemic situation is not in control due to non-availability of medicines.

10.
Soft comput ; 25(18): 12551-12563, 2021.
Article in English | MEDLINE | ID: covidwho-1317556

ABSTRACT

Presently, novel coronavirus outbreak 2019 (COVID-19) is a major threat to public health. Mathematical epidemic models can be utilized to forecast the course of an epidemic and cultivate approaches for controlling it. This paper utilizes the real data of spreading COVID-19 in Saudi Arabia for mathematical modeling and complex analyses. This paper introduces the Susceptible, Exposed, Infectious, Recovered, Undetectable, and Deceased (SEIRUD) and Machine learning algorithm to predict and control COVID-19 in Saudi Arabia.This COVID-19 has initiated many methods, such as cloud computing, edge-computing, IoT, artificial intelligence. The use of sensor devices has increased enormously. Similarly, several developments in solving the COVID-19 crisis have been used by IoT applications. The new technology relies on IoT variables and the roles of symptoms using wearable sensors to forecast cases of COVID-19. The working model involves wearable devices, occupational therapy, condition control, testing of cases, suspicious and IoT elements. Mathematical modeling is useful for understanding the fundamental principle of the transmission of COVID-19 and providing guidance for possible predictions. The method suggested predicts whether COVID-19 would expand or die in the long term in the population. The mathematical study results and related simulation are described here as a way of forecasting the progress and the possible end of the epidemic with three forms of scenarios: 'No Action,' 'Lockdowns and New Medicine.' The lock case slows it down the peak by minimizing infection and impacts area equality of the infected deformation. This study familiarizes the ideal protocol, which can support the Saudi population to breakdown spreading COVID-19 in an accurate and timely way. The simulation findings have been executed, and the suggested model enhances the accuracy ratio of 89.3%, prediction ratio of 88.7%, the precision ratio of 87.7%, recall ratio of 86.4%, and F1 score of 90.9% compared to other existing methods.

11.
EClinicalMedicine ; 38: 101020, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1313060

ABSTRACT

BACKGROUND: ZyCoV-D is a DNA vaccine candidate, which comprises a plasmid DNA carrying spike-S gene of SARS-CoV-2 virus along with gene coding for signal peptide. The spike(S) region includes the receptor-binding domain (RBD), which binds to the human angiotensin converting Enzyme (ACE)-2 receptor and mediates the entry of virus inside the cell. METHODS: We conducted a single-center, open-label, non-randomized, Phase 1 trial in India between July 2020 and October 2020. Healthy adults aged between 18 and 55 years were sequentially enrolled and allocated to one of four treatment arms in a dose escalation manner. Three doses of vaccine were administered 28 days apart and each subject was followed up for 28 days post third dose to evaluate safety and immunogenicity. FINDINGS: Out of 126 individuals screened for eligibility. Forty-eight subjects (mean age 34·9 years) were enrolled and vaccinated in the Phase 1 study Overall, 12/48 (25%) subjects reported at least one AE (i.e. combined solicited and unsolicited) during the study. There were no deaths or serious adverse events reported in Phase 1 of the study. The proportion of subjects who seroconverted based on IgG titers on day 84 was 4/11 (36·36%), 4/12 (33·33%), 10/10 (100·00%) and 8/10 (80·00%) in the treatment Arm 1 (1 mg: Needle), Arm 2 (1 mg: NFIS), Arm 3 (2 mg: Needle) and Arm 4 (2 mg: NFIS), respectively. INTERPRETATION: ZyCoV-D vaccine is found to be safe, well-tolerated and immunogenic in the Phase 1 trial. Our findings suggest that the DNA vaccine warrants further investigation.

12.
J Infect Public Health ; 14(7): 817-831, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1193398

ABSTRACT

Coronaviruses did not invite attention at a global level and responsiveness until the series of 2003-SARS contagion followed by year-2012 MERS plus, most recently, 2019-nCoV eruptions. SARS-CoV &MERS-CoV are painstaking, extremely pathogenic. Also, very evidently, both have been communicated from bats to palm-civets & dromedary camels and further transferred ultimately to humans. No country has been deprived of this viral genomic contamination wherever populaces reside and are interconnected. This study aimed to develop a mathematical model for calculating the transmissibility of this viral genome. The analysis aids the study of the outbreak of this Virus towards the other parts of the continent and the world. The parameters such as population mobility, natural history, epidemiological characteristics, and the transmission mechanism towards viral spread when considered into crowd dynamism result in improved estimation. This article studies the impact of time on the amount of susceptible, exposed, the infected person taking into account asymptomatic and symptomatic ones; recovered i.e., removed from this model and the virus particles existing in the open surfaces. The transition from stable phase to attractor phase happens after 13 days i.e.; it takes nearly a fortnight for the spread to randomize among people. Further, the pandemic transmission remains in the attractor phase for a very long time if no control measures are taken up. The attractor-source phase continues up to 385 days i.e., more than a year, and perhaps stabilizes on 386th day as per the Lyapunov exponent's analysis. The time series helps to know the period of the Virus's survival in the open sources i.e. markets, open spaces and various other carriers of the Virus if not quarantined or sanitized. The Virus cease to exist in around 60 days if it does not find any carrier or infect more places, people etc. The changes in LCEs of all variables as time progresses for around 400 days have been forecasted. It can be observed that phase trajectories indicate how the two variables interact with each other and affect the overall system's dynamics. It has been observed that for exposed and asymptomatically infected (y-z), as exposed ones (y) change from 0 to 100 the value of asymptomatically infected (z) increased upto around 58, at exposed ones (y)=100, asymptomatically infected (z) has two values as 58 and 10 i.e. follows bifurcation and as exposed ones (y) changes values upto 180, the value of asymptomatically infected (z) decreases to 25 so for exposed ones (y) from 100 to 180, asymptomatically infected (z) varies from 58 to 25 to 10 follows bifurcation. Also, phase structures of exposed-symptomatically infected (y-u), exposed-removed (y-v), exposed-virus in the reservoir (y-w), asymptomatically infected-removed (z-v), symptomatically infected-removed (u-v) specifically depict bifurcations in various forms at different points. In case of asymptomatically infected-virus in the reservoir (z-w), at asymptomatically infected (z)=10, the value of viruses in the reservoir (w)=50, then as asymptomatically infected (z) increases to upto around 60. At this point, removed ones (v) increase from 50 to 70 and asymptomatically infected (z) decrease to 20 i.e., crosses the same value twice, which shows its limiting is known as limit cycle behavior and both the values tend to decrease towards zero. It shows a closed-loop limit cycle. Today, there has been no scientific revolution in the development of vaccination, nor has any antiviral treatment been successful, resulting in lack of its medication. Based on the phases, time series, and complexity analysis of the model's various parameters, it is studied to understand the variation in this pandemic's scenario.


Subject(s)
COVID-19 , SARS Virus , Humans , Nonlinear Dynamics , Pandemics , SARS-CoV-2
14.
Heliyon ; 7(4): e06657, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1163819

ABSTRACT

AIMS: COVID-19 has currently emerged as the major global pandemic affecting the lives of people across the globe. It broke out from Wuhan Province of China, first reported to WHO on 31st December 2019 as "Pneumonia of unknown cause". Over time more people were infected with this virus, and the only tactic to ensure safety was to take precautionary measures due to the lack of any effective treatment or vaccines. As a result of unavailability of desired efficacy for previously repurposed drugs, exploring novel scaffolds against the virus has become the need of the hour. MAIN METHODS: In the present study, 23 new annomontine analogues were designed representing ß-Carboline based scaffolds. A hypothesis on its role as an effective ligand was laid for target-specific binding in SARS-CoV-2. These molecules were used for molecular docking analysis against the multiple possible drug targets using the Maestro Interface. To ensure the drug safety of these molecules ADME/Tox analysis was also performed. KEY FINDINGS: The molecular docking analysis of the 23 novel molecules indicated the efficiency of these derivates against COVID-19. The efficiency of molecules was computed by the summation of the docking score against each target defined as LigE Score and compared against Hydroxycholoquine as a standard. Based on the docking score, the majority of the annomontine derivatives were found to have increased binding affinity with targets as compared to hydroxycholoquine. SIGNIFICANCE: Due to the lack of efficiency, effectiveness, and failure of already repurposed drugs against the COVID-19, the exploration of the novel scaffold that can act as effective treatment is much needed. The current study hence emphasizes the potential of Annomontine based - ß- Carboline derivatives as a potential drug candidate against COVID-19.

15.
Hosp Pract (1995) ; 49(3): 151-154, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1066189

ABSTRACT

COVID-19 pandemic has devastated large urban areas across the country. Most rural areas have so far been able to avoid the initial surge in cases due to the low population density. However, as the pandemic advances, rural areas are at an increased risk for the second wave of the epidemic. Rural areas are especially vulnerable due to the older population, higher comorbidities, and lack of access to healthcare. This field report discusses the experiences and issues faced by the rural Appalachian community during the ongoing COVID-19 pandemic.


Subject(s)
COVID-19/therapy , Health Services Accessibility/statistics & numerical data , Pneumonia, Viral/therapy , Rural Health Services/organization & administration , Rural Population/statistics & numerical data , Appalachian Region , Humans
16.
Anatolia ; : 1-15, 2021.
Article in English | Taylor & Francis | ID: covidwho-1054179
17.
Ann Am Thorac Soc ; 17(11): 1343-1351, 2020 11.
Article in English | MEDLINE | ID: covidwho-922719

ABSTRACT

Background: In March 2020, many elective medical services were canceled in response to the coronavirus disease 2019 (COVID-19) pandemic. The daily case rate is now declining in many states and there is a need for guidance about the resumption of elective clinical services for patients with lung disease or sleep conditions.Methods: Volunteers were solicited from the Association of Pulmonary, Critical Care, and Sleep Division Directors and American Thoracic Society. Working groups developed plans by discussion and consensus for resuming elective services in pulmonary and sleep-medicine clinics, pulmonary function testing laboratories, bronchoscopy and procedure suites, polysomnography laboratories, and pulmonary rehabilitation facilities.Results: The community new case rate should be consistently low or have a downward trajectory for at least 14 days before resuming elective clinical services. In addition, institutions should have an operational strategy that consists of patient prioritization, screening, diagnostic testing, physical distancing, infection control, and follow-up surveillance. The goals are to protect patients and staff from exposure to the virus, account for limitations in staff, equipment, and space that are essential for the care of patients with COVID-19, and provide access to care for patients with acute and chronic conditions.Conclusions: Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a dynamic process and, therefore, it is likely that the prevalence of COVID-19 in the community will wax and wane. This will impact an institution's mitigation needs. Operating procedures should be frequently reassessed and modified as needed. The suggestions provided are those of the authors and do not represent official positions of the Association of Pulmonary, Critical Care, and Sleep Division Directors or the American Thoracic Society.


Subject(s)
Coronavirus Infections/prevention & control , Critical Care , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pulmonary Medicine , Sleep , Advisory Committees , Betacoronavirus , COVID-19 , Consensus , Coronavirus Infections/diagnosis , Humans , Pneumonia, Viral/diagnosis , SARS-CoV-2 , Societies, Medical , United States
19.
J Racial Ethn Health Disparities ; 7(5): 817-821, 2020 10.
Article in English | MEDLINE | ID: covidwho-639259

ABSTRACT

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has ravaged many urban and high-density areas in the USA. However, rural areas (despite their low population density) may be especially vulnerable to poor outcomes from COVID-19, owing to limited healthcare infrastructure, long distances to advanced health care, and population characteristics (e.g., high tobacco use, hypertension, obesity, older age). A panel of experts who are actively engaged in treating and managing COVID-19 at a rural academic center was convened to address this topic. In this commentary, we provide readers with some specific issues faced by rural healthcare providers and offer guidance in overcoming these challenges. This guidance includes alternative ventilator strategies, personal protective equipment (PPE), and common therapeutic options.


Subject(s)
Coronavirus Infections/therapy , Medically Underserved Area , Pandemics , Pneumonia, Viral/therapy , Practice Guidelines as Topic , Rural Health Services , COVID-19 , Coronavirus Infections/epidemiology , Humans , Personal Protective Equipment , Pneumonia, Viral/epidemiology , Respiration, Artificial/methods , United States/epidemiology
20.
Cureus ; 12(4): e7849, 2020 Apr 27.
Article in English | MEDLINE | ID: covidwho-487792

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a respiratory illness caused by the highly infectious novel SARS-CoV-2 coronavirus spread by droplet transmission. Consequently, the use of respiratory devices that may potentially promote aerosolization like non-invasive positive pressure ventilation (NIPPV) for diseases such as obstructive sleep apnea (OSA), advanced chronic obstructive lung disease, pulmonary hypertension (PH), and neuromuscular respiratory disease has been called into question. We present a case of a patient with history of OSA and PH convalescing from refractory acute respiratory distress syndrome (ARDS) secondary to COVID-19 who was successfully extubated to average volume-assured pressure support (AVAPS). A 74-year-old male with medical history notable for OSA on NIPPV, PH, and hypertension presented with respiratory failure secondary to COVID-19 confirmed on polymerase chain reaction (PCR) test. His respiratory status worsened leading to ARDS requiring intubation. He was initially extubated to high flow nasal cannula (HFNC) due to hospital policy to avoid NIPPV due to concerns of viral dissemination. He did not tolerate HFNC and required re-intubation for prolonged period. He was then medically optimized for a second attempt and extubated two days later to AVAPS with an anti-viral filter and negative pressure room with a goal of optimizing his critical illness myopathy and pre-existing OSA and PH. He tolerated extubation well, and over the next five days was weaned from alternating AVAPS/HFNC to eventually requiring two liters nasal cannula in the day and AVAPS mode at night. This case highlights a potential therapeutic option for patients with severe respiratory failure secondary to COVID-19. This patient's pre-existing comorbidities of OSA and PH markedly increased his risk for extubation failure on HFNC. The use of AVAPS after his second extubation attempt helped ensure ventilation and oxygenation non-invasively. COVID-19 can lead to prolonged dependence on mechanical ventilation. This pandemic has the potential to create medical resource scarcities, especially in rural areas where ventilators and trained personnel are already in short supply. By using AVAPS mode, this patient was able to rehabilitate his myopathy and participate in intermittent weaning of HFNC to ultimately simple nasal cannula. AVAPS is useful tool to facilitate extubation, as it allows non-invasive support of respiratory dynamics, particularly in those with co-morbidities such as OSA and PH. Further, larger scale studies are needed to determine its exact role during the COVID-19 pandemic.

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