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1.
Swiss Med Wkly ; 152: w30212, 2022 08 29.
Article in English | MEDLINE | ID: covidwho-2202462

ABSTRACT

AIMS OF THE STUDY: Awake prone positioning (aPP) in non-intubated patients with severe SARS-CoV-2-related pneumonia improves oxygenation and reduces the intubation rate, but no early predictors for success or failure of the strategy have been described. The main objective of this study was to assess whether response to the first aPP in terms of PaO2/FiO2, alveolar-arterial gradient (Aa-O2), respiratory rate and PaCO2 could predict the need for intubation. As secondary objective, we assessed the effects of aPP on the same parameters for all the sessions considered together. METHODS: Retrospective analysis of consecutive SARS-CoV-2 pneumonia patients suffering from acute respiratory failure with moderate to severe hypoxaemia for whom aPP was performed for at least 45 minutes based on the prescription of the clinician in charge according to predefined criteria. Respiratory rate, blood gases and oxygenation parameters (PaO2/FiO2 and Aa-O2), before and after the first aPP were compared between patients who were subsequently intubated or not. Effects of all the aPP sessions together were also analysed. RESULTS: One hundred and sixty-six patients were admitted for SARS-CoV-2 pneumonia during the study period. Among them, 50 received aPP lasting at least 45 minutes. Because 17 denied consent for data analysis and 2 were excluded because of a "do not intubate order", 31 patients (for a total of 116 aPP sessions without any severe adverse events reported) were included. Among them, 10 (32.3%) were intubated. Mean age ± standard deviation (SD) was 60 ± 12 years. At ICU admission, respiratory rate was 26 ± 7/minute, median PaO2/FiO2 94 (interquartile range [IQR] 74-116) mm Hg and median Aa-O2 412 (IQR 286-427) mm Hg (markedly increased). Baseline characteristics did not statistically differ between patients who subsequently needed intubation or not. During the first aPP, PaO2/FiO2 increased and Aa-O2 decreased. When comparing patients who later where intubated or not, we observed, in the non intubated group only, a clinically significant decrease in median Aa-O2, from 294 (280-414) to 204 (107-281) mm Hg, corresponding to a 40% (26-56%) reduction, and a PaO2/FiO2 increase, from 103 (84-116) to 162 (138-195), corresponding to an increase of 48% (11-93%). The p value is <0.005 for both. When all the aPP sessions (n = 80) were considered together, aPP was associated with a significant increase in PaO2/FiO2 from 112 (80-132) to 156 (86-183) mm Hg (p <0.001) and Aa-O2 decrease from 304 (244-418) to 224 (148-361) mm Hg (p = 0.001). CONCLUSIONS: Awake pronation in spontaneously breathing patients is feasible, and improves PaO2/FiO2 and Aa-O2. Response to the first session seems to be associated with lower intubation rate.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Respiratory Insufficiency , COVID-19/complications , COVID-19/therapy , Humans , Hypoxia/complications , Hypoxia/therapy , Intubation, Intratracheal/adverse effects , Prone Position , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Retrospective Studies , SARS-CoV-2 , Wakefulness
2.
Clin Chest Med ; 43(3): 519-528, 2022 09.
Article in English | MEDLINE | ID: covidwho-2177066

ABSTRACT

Extracorporeal life support (ECLS) has a role in different types of respiratory failure including acute respiratory distress syndrome (ARDS), decompensated pulmonary hypertension, bridge to lung transplantation, and primary graft dysfunction after lung transplantation. ECLS in ARDS allows for lung-protective ventilation with the goal to reduce the risk of ventilator-induced lung injury. ECLS use in severe ARDS should be considered when conventional management strategies are not sufficient to safely support gas exchange. More research is needed to identify optimal mechanical ventilation during ECLS, weaning ECLS support, strategies for mobilization, sedation and anticoagulation, and long-term outcomes post-ECLS.


Subject(s)
Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome , Respiratory Insufficiency , Anticoagulants , Humans , Respiration, Artificial/adverse effects , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy
3.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2508557.v1

ABSTRACT

Background: The particle structure of Emiliania huxleyi virus (EhV), an algal infecting member of nucleocytoplasmic large DNA viruses (NCLDVs), contains an outer lipid membrane envelope similar to that found in animal viruses such as African swine fever virus (ASFV). Despite both being enveloped NCLDVs, EhV and ASFV are known for their stability in the environment. Method: Here we report for the first time, the application of a viability PCR method to describe the unprecedented and similar virion thermal stability of both EhV and ASFV. This result contradicts the bioassay method that suggests that virus “infectivity” is lost in a matter of seconds (EhV) and minutes (ASFV) at temperature greater than 50 °C. Confocal microscopy and analytical flow cytometry methods was used to validate the viability PCR data for EhV. Results: We observed that both EhV and ASFV particles has unprecedented thermal tolerances. These two NCLDVs are exceptions to the rule that having an enveloped virion anatomy is a predicted weakness, as is often observed in enveloped RNA viruses (i.e., the viruses causing Porcine Reproductive and Respiratory Syndrome (PRRS), COVID-19, Ebola, or seasonal influenza). Using the viability PCR method, we confirm that no PRRSV particles remain after 20 minutes of exposure to temperatures up to 100 °C. Conclusions: This observation has practical implications for industries involved in animal health and food security. Finally, we propose that EhV could be used as a surrogate for ASFV under certain circumstances.


Subject(s)
59585 , 5444 , 32931 , 12552 , 21079 , 32676
4.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.01.16.524211

ABSTRACT

Children infected with SARS-CoV-2 rarely progress to respiratory failure, but the risk of mortality in infected people over 85 years of age remains high, despite vaccination and improving treatment options. Here, we take a comprehensive, multidisciplinary approach to investigate differences in the cellular landscape and function of paediatric (<11y), adult (30-50y) and elderly (>70y) nasal epithelial cells experimentally infected with SARS-CoV-2. Our data reveal that nasal epithelial cell subtypes show different tropism to SARS-CoV-2, correlating with age, ACE2 and TMPRSS2 expression. Ciliated cells are a viral replication centre across all age groups, but a distinct goblet inflammatory subtype emerges in infected paediatric cultures, identifiable by high expression of interferon stimulated genes and truncated viral genomes. In contrast, infected elderly cultures show a proportional increase in ITGB6hi progenitors, which facilitate viral spread and are associated with dysfunctional epithelial repair pathways. A video explaining this work can be found here - https://youtu.be/uExP4bx6D_A .


Subject(s)
7414 , 12552 , 52116
5.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.01.10.23284397

ABSTRACT

Background: We estimated combined protection conferred by prior SARS-CoV-2 infection and COVID-19 vaccination against COVID-19-associated acute respiratory illness (ARI). Methods: During SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant circulation between October 2021 and April 2022, prospectively enrolled adult patients with outpatient ARI had respiratory and filter paper blood specimens collected for SARS-CoV-2 molecular testing and serology. Dried blood spots were tested for immunoglobulin-G antibodies against SARS-CoV-2 nucleocapsid (NP) and spike protein receptor binding domain antigen using a validated multiplex bead assay. Evidence of prior SARS-CoV-2 infection also included documented or self-reported laboratory-confirmed COVID-19. We used documented COVID-19 vaccination status to estimate vaccine effectiveness (VE) by multivariable logistic regression by prior infection status. Results: 455 (29%) of 1577 participants tested positive for SARS-CoV-2 infection at enrollment; 209 (46%) case-patients and 637 (57%) test-negative patients were NP seropositive, had documented previous laboratory-confirmed COVID-19, or self-reported prior infection. Among previously uninfected patients, three-dose VE was 97% (95% confidence interval [CI], 60%, 99%) against Delta, but not statistically significant against Omicron. Among previously infected patients, three-dose VE was 57% (CI, 20%, 76%) against Omicron; VE against Delta could not be estimated. Conclusions: Three mRNA COVID-19 vaccine doses provided additional protection against SARS-CoV-2 Omicron variant-associated illness among previously infected participants.


Subject(s)
59585 , 12552
6.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.01.01.522064

ABSTRACT

Clinical manifestations of COVID-19 vary widely, ranging from asymptomatic to severe respiratory failure with profound inflammation. Although risk factors for severe illness have been identified, definitive determinants remain elusive. Clonal hematopoiesis (CH), the expansion of hematopoietic stem and progenitor cells bearing acquired somatic mutations, is associated with advanced age and hyperinflammation. Given the similar age range and hyperinflammatory phenotype between frequent CH and severe COVID-19, CH could impact the risk of severe COVID-19. Human cohort studies have attempted to prove this relationship, but conclusions are conflicting. Rhesus macaques (RMs) are being utilized to test vaccines and therapeutics for COVID-19. However, RMs, even other species, have not yet been reported to develop late inflammatory COVID-19 disease. Here, RMs with either spontaneous DNMT3A or engineered TET2 CH along with similarly transplanted and conditioned controls were infected with SARS-CoV-2 and monitored until 12 days post-inoculation (dpi). Although no significant differences in clinical symptoms and blood counts were noted, an aged animal with natural DNMT3A CH died on 10 dpi. CH macaques showed evidence of sustained local inflammatory responses compared to controls. Interestingly, viral loads in respiratory tracts were higher at every timepoint in the CH group. Lung sections from euthanasia showed evidence of mild inflammation in all animals, while viral antigen was more frequently detected in the lung tissues of CH macaques even at the time of autopsy. Despite the lack of striking inflammation and serious illness, our findings suggest potential pathophysiological differences in RMs with or without CH upon SARS-CoV-2 infection.


Subject(s)
30170 , 59585 , 12552 , 7426
7.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.12.28.22283971

ABSTRACT

Introduction: The COVID 19 pandemic was highlighted by a rise in hospital admissions secondary to respiratory decompensation. This was accompanied by an increase in ICU admissions, endotracheal intubation and mechanical ventilation. As a consequence, tracheostomies became essential in preventing complications of prolonged intubation and to facilitate weaning from sedation and mechanical ventilation. With the lack of international consensus on tracheostomy technique and optimal timing, we present our experience with 377 percutaneous tracheostomies performed on critically ill COVID 19 patients. Objective: To report the outcomes of critically ill patients with COVID 19 who underwent percutaneous tracheostomy during a period of 24 months. Methods: A retrospective single-center electronic chart review was performed on all ICU patients who underwent percutaneous tracheostomy after respiratory failure secondary to COVID 19 between March 2020 to March 2022. Results: A total of 377 percutaneous tracheostomies were performed. The mean duration between intubation and percutaneous tracheostomy was 17.4 days (3 to 61). The study included 222 males (59%) and 155 females (41%). The mean age of patients was 56.2 years (17-94), with a mean BMI was 31.3 (14 to 68). The commonest comorbidities among patients were diabetes mellitus (50%) and hypertension (48%). Complications were encountered in 85 cases (23%), with the commonest overall complication being minor bleeding. 203 patients (54%) were weaned from sedation. The mean duration between tracheostomy and weaning from sedation was 7.5 days (1 to 47 days). 156 patients (41%) were weaned from MV. The mean duration between tracheostomy and weaning from MV was 12.9 days (1 to 58 days). There was a total of 236 (63%) deaths reported during the period of this study. No deaths were attributable to the surgical procedure. Conclusion: Percutaneous tracheostomy can be safely performed in patients with COVID 19. With lack of conclusive objective data regarding the optimal timing for tracheostomy, we recommend that tracheostomy be performed as soon as possible after the 7th day endotracheal intubation. Key Words: Percutaneous tracheostomy, COVID 19, Critically ill, ICU


Subject(s)
30170 , 59585 , 6622 , 7152 , 3660 , 12552 , 3942
9.
Adv Exp Med Biol ; 1353: 173-195, 2021.
Article in English | MEDLINE | ID: covidwho-2157941

ABSTRACT

INTRODUCTION: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently and rapidly emerged and developed into a global pandemic. In SARS-CoV-2 patients with refractory respiratory failure, there may be a role for veno-venous extracorporeal membrane oxygenation (V-V ECMO) as a life-saving rescue intervention. METHODS: This review summarizes the evidence gathered until June 12, 2020; electronic databases were screened for pertinent reports on coronavirus and V-V ECMO. Search was conducted by two independent investigators; keywords used were SARS-CoV-2, COVID-19, ECMO, and extracorporeal life support (ECLS). RESULTS: Many patients with COVID-19 experience moderate symptoms and a relatively quick recovery, but others must be admitted into the intensive care unit due to severe respiratory failure and often must be mechanically ventilated. Further deterioration may require institution of extracorporeal oxygenation. Infection mechanisms may trigger "cytokine storm," an inflammatory disorder notable for multi-organ system failure; together with other metabolic and hematological changes, these amplify the changes pertinent to ECMO therapy, often exaggerating blood coagulation disorders. Thirty-two studies were found describing experiences with ECMO in the treatment of COVID-19. Of 4,912 COVID-19 patients, 2,119 (43%) developed ARDS and 2,086 (42%) were transferred to the ICU; 1,015 patients (21%) were treated with ECMO. While in an overall cohort, observed mortality was 640 (13%), the mortality within ECMO subgroups reached up to 34.6% (range 0-100%). CONCLUSION: The efficacy of ECMO treatment for COVID-19 is largely dependent on the expertise of the center in ECLS due to the interplay between the changes in hematological and inflammatory modulators associated with both COVID-19 and ECMO. In order to support gas exchange during early infection with SARS-CoV-2, ECMO has a strong rationale for the treatment of the most critically ill patients. Due to the limited resources during a global pandemic, ECMO should be reserved for only the most severe cases of COVID-19.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Respiratory Insufficiency , Humans , Pandemics , Respiratory Insufficiency/therapy , SARS-CoV-2
11.
J Pharmacol Exp Ther ; 381(2): 129-136, 2022 05.
Article in English | MEDLINE | ID: covidwho-2152871

ABSTRACT

The incidence of fatal drug overdoses in the United States is an alarming public health threat that has been exacerbated by the COVID-19 pandemic, resulting in over 100,000 deaths between April 2020 and April 2021. A significant portion of this is attributable to widespread access to fentanyl and other synthetic opioids, alone or in combination with heroin or psychostimulants, such as cocaine or methamphetamine. Monoclonal antibodies (mAb) offer prophylactic and therapeutic interventions against opioid overdose by binding opioids in serum, reducing distribution of drug to the brain and other organs. Here, we investigated the efficacy of a leading antifentanyl mAb, clone HY6-F9, in reversal and prevention of fentanyl-induced toxicity compared with the opioid receptor antagonist naloxone (NLX) in rats. In postexposure models, rats were challenged with fentanyl, followed by HY6-F9, NLX, or both. HY6-F9 reversed fentanyl-induced antinociception, respiratory depression, and bradycardia, and rats retained protection against additional challenges for at least 1 week. Although intravenous NLX reversed fentanyl-induced respiratory depression more rapidly than mAb alone, kinetics of reversal by intravenous mAb were similar to subcutaneous NLX. Coadministration of mAb and NLX provided greater protection than individual treatments against high doses of fentanyl. Prophylactic administration of mAb reduced the ED50 of NLX approximately twofold against 2.25 mg/kg of fentanyl. Finally, mAb sequestered fentanyl and its metabolite norfentanyl in serum and reduced brain concentrations of fentanyl. These results support the translation of mAb as medical interventions alone or in combination with NLX to prevent and reverse fentanyl-related overdose. SIGNIFICANCE STATEMENT: Fentanyl-related overdoses have increased dramatically in the US and worldwide. Currently, approved pharmacotherapies for treatment of opioid use disorder and reversal of overdose are not sufficient to curb the incidence of opioid-related deaths. Additionally, fentanyl and its potent analogs present a potential risk from use in deliberate poisoning or chemical attacks. This study demonstrates the use of monoclonal antibodies as a countermeasure to fentanyl-induced toxicity in pre- and postexposure scenarios, supporting their use in combination with the opioid antagonist naloxone.


Subject(s)
COVID-19 , Drug Overdose , Respiratory Insufficiency , Analgesics, Opioid/therapeutic use , Animals , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Drug Overdose/drug therapy , Fentanyl , Humans , Naloxone/pharmacology , Naloxone/therapeutic use , Narcotic Antagonists/pharmacology , Pandemics , Rats , Respiratory Insufficiency/drug therapy
12.
Curr Opin Crit Care ; 28(6): 660-666, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2152245

ABSTRACT

PURPOSE OF REVIEW: To review the clinical problem and noninvasive treatments of hypoxemia in critically-ill patients with coronavirus disease 2019 pneumonia and describe recent advances in evidence supporting bedside decision making. RECENT FINDINGS: High-flow nasal oxygen and noninvasive ventilation, along with awake prone positioning are potentially helpful therapies for acute hypoxemic respiratory failure. High-flow nasal oxygen therapy has been widely implemented as a form of oxygen support supported by prepandemic randomized controlled trials showing possible benefit over noninvasive ventilation. Given the sheer volume of patients, noninvasive ventilation was often required, and based on a well conducted randomized controlled trial there was a developing role for helmet-interface noninvasive. Coupled with noninvasive supports, the use of awake prone positioning demonstrated physiological benefits, but randomized controlled trial data did not demonstrate clear outcome superiority. SUMMARY: The use of noninvasive oxygen strategies and our understanding of the proposed mechanisms are evolving. Variability in patient severity and physiology may dictate a personalized approach to care. High-flow nasal oxygen may be paired with awake and spontaneously breathing prone-positioning to optimize oxygen and lung mechanics but requires further insight before widely applying to clinical practice.


Subject(s)
COVID-19 , Noninvasive Ventilation , Respiratory Insufficiency , Humans , COVID-19/therapy , Respiratory Insufficiency/therapy , Oxygen Inhalation Therapy , Hypoxia/therapy , Oxygen , Critical Care , Lung , Randomized Controlled Trials as Topic
13.
BMC Pulm Med ; 22(1): 227, 2022 Jun 13.
Article in English | MEDLINE | ID: covidwho-1885300

ABSTRACT

BACKGROUND: This study was designed to explore the early predictive value of the respiratory rate oxygenation (ROX) index modified by PaO2 (mROX) in high-flow nasal cannula (HFNC) therapy in patients with acute hypoxemia respiratory failure (AHRF). METHOD: Seventy-five patients with AHRF treated with HFNC were retrospectively reviewed. Respiratory parameters at baseline and 2 h after HFNC initiation were analyzed. The predictive value of the ROX (ratio of pulse oximetry/FIO2 to respiratory rate) and mROX (ratio of arterial oxygen /FIO2 to respiratory rate) indices with two variations by adding heart rate to each index (ROX-HR and mROX-HR) was evaluated. RESULTS: HFNC therapy failed in 24 patients, who had significantly higher intensive care unit (ICU) mortality and longer ICU stay. Both the ROX and mROX indices at 2 h after HFNC initiation can predict the risk of intubation after HFNC. Two hours after HFNC initiation, the mROX index had a higher area under the receiver operating characteristic curve (AUROC) for predicting HFNC success than the ROX index. Besides, baseline mROX index of greater than 7.1 showed a specificity of 100% for HFNC success. CONCLUSION: The mROX index may be a suitable predictor of HFNC therapy outcomes at the early phase in patients with AHRF.


Subject(s)
Noninvasive Ventilation , Respiratory Insufficiency , Blood Gas Analysis , Cannula , Humans , Oxygen Inhalation Therapy , Respiratory Insufficiency/therapy , Respiratory Rate , Retrospective Studies
14.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.12.23.22283897

ABSTRACT

Introduction: Historic disruption in health infrastructure combined with data from a recent vaccine coverage survey suggests there are likely significant immunity gaps to vaccine preventable diseases and high risk of outbreaks in Timor-Leste. Community-based serological surveillance is an important tool to augment understanding of population-level immunity achieved through vaccine coverage and/or derived from prior infection. Methods and analysis: This national population-representative serosurvey will take a three-stage cluster sample and aims to include 5600 individuals above one year of age. Serum samples will be collected by phlebotomy and analysed for measles immunoglobulin G (IgG), rubella IgG, severe acute respiratory syndrome coronavirus-2 anti-spike protein IgG, hepatitis B surface antibody and hepatitis B core antigen using commercially available chemiluminescent immunoassays or enzyme-linked immunosorbent assays. In addition to crude prevalence estimates and to account for differences in Timor-Leste age structure, we will calculate stratified age-standardised prevalence estimates, using Asia in 2013 as the standard population. Additionally, this survey will derive a national asset of serum and dried blood spot samples which can be used for further investigation of infectious disease sero-epidemiology and/or validation of existing and novel serological assays for infectious diseases. Ethics and dissemination: Ethical approval has been obtained from the Research Ethics and Technical Committee of the Instituto Nacional da Saude,Timor-Leste and the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research, Australia. Co-designing this study with Timor-Leste Ministry-of-Health and other relevant partner organisations will allow immediate translation of findings into public health policy (which may include changes to routine immunisation service delivery and/or plans for supplementary immunisation activities).


Subject(s)
6664 , 53500 , 28582 , 12784 , 12552
15.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2408451.v1

ABSTRACT

Background This systematic review aims to summarise the evidence regarding any benefits of high flow nasal oxygen (HFNO) therapy compared to conventional oxygen therapy (COT) in hospitalised patients with acute or chronic respiratory illnesses.Methods A comprehensive search was performed across three databases for studies that reported any of: escalation to invasive mechanical ventilation (IMV), mortality, length of stay, carbon dioxide levels, disability, or admission rates.Results In patients with acute respiratory illnesses, pooled RCT data revealed no significant differences between HFNO and COT in overall need for IMV (RR = 0.82, 95% CI = 0.65–1.05; p = 0.11; n = 15 RCTs) or in-hospital mortality (RR = 1.00, 95% CI 0.85–1.17; p = 1.00; n = 5). Similarly, for patients with chronic respiratory illnesses, RCT data revealed no significant difference in overall need for IMV (RR = 0.86, 95% CI = 0.33–2.23; p = 0.76; n = 4) or in-hospital mortality (RR = 0.40, 95% CI = 0.04–4.10; p = 0.44; n = 1) for HFNO compared to COT. Patients with COVID-19 receiving HFNO had a significantly reduced need for IMV (RR = 0.72, 95% CI = 0.63–0.82; p < 0.001), short-term mortality (RR = 0.62, 95% CI = 0.48–0.79; p < 0.001), and long-term mortality (RR = 0.67, 95% CI = 0.48–0.92; p = 0.01).Conclusion HFNO did not significantly reduce the need for IMV escalation or in-hospital mortality in patients with acute or chronic respiratory illnesses, except for patients with COVID-19.


Subject(s)
12552 , 59585 , 37050 , 9554
16.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.12.22.22283763

ABSTRACT

Background: Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) is a highly transmissible virus causing Coronavirus disease (COVID-19). Its key symptoms include fever, dry cough, and shortness of breath. Vaccine plays a significant role in controlling infectious disease, and reduction of the use of health service leaving more resources for the treatment of other diseases.2 Vero Cell is an inactivated vaccine against COVID-19 manufactured by Sinopharm Company of China and recommended for people above 18 years by the World Health Organization. It is administered in two doses of 0.5 ml, 14-28 days apart. Methods and findings: A prospective cross-sectional study was conducted among undergraduate medical students and intern doctors of Nepalgunj Medical College after receiving ethical approval from the institutional review committee of this college. Demographic features of the study population and the frequency and percentages of side effects among the population who received the vaccines were calculated along with the duration of symptoms. All undergraduate medical students and intern doctors of Nepalgunj Medical College who received two doses of the Vero Cell vaccine against COVID-19 were involved in the study. Those who failed to give written consent and those who were not willing to receive both doses of vaccine were excluded. Data were collected using a self-administered structured questionnaire. The eligible participants were provided with the questionnaire twice, after administration of each dose of vaccine. Collected data were entered in structured Pro-forma and analyzed statistically in Microsoft Excel 2019 MSO (Version 2021). About 75% of the participants had one or more symptoms after the first dose of the vaccine, which reduced to 62% after the second dose. Symptoms were more in males after the first dose (76% vs. 72%), but the reverse was seen after the second dose (54% vs. 77%). Pain at the injection site was the most commonly reported side effect (27%) followed by myalgia (20%). No individuals receiving both doses of vaccine had diarrhea, difficulty in breathing, tingling sensation, or anaphylactic reaction. A higher percentage of females experienced pain at the injection site after the second dose over the first than males. However, males experienced fatigue more than females after every dose. Pain at the injection site and Myalgia were common symptoms to start early, within 12 hours post-vaccination. However, fatigue was seen maximally 24 hrs post-vaccination. Fever was seen in 7% of participants within 12 hours of vaccination. Cough and sore throat as side effects persisted up to 2 weeks after vaccination. The main limitation of the study is the low sample size. Conclusions: Pain at the injection site was the most common AEFI followed by Myalgia with other insignificant effects. There were no life-threatening side effects. A larger study on the general population including all age groups is highly recommended to detect all spectrum of side effects.


Subject(s)
3386 , 31543 , 28582 , 59585 , 10333 , 4479 , 3994 , 5444 , 12552 , 55208 , 10481 , 5325
17.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2400971.v1

ABSTRACT

The currently dominant Omicron variant of the severe acute respiratory syndrome 2 (SARS-CoV-2) has swiftly diverged into clades. To predict the probable impact of clades, the consensus insertions/deletions (indels) and amino acid substitutions of the whole genome of clades were compared with original SARS-CoV-2. The indels and polymorphic amino acids were clade specific or shared among clades. The 21K clade has unique indels and substitutions, which probably represents reverted indels/substitutions. Three observed probable indirect evidences of SARS-CoV-2 attenuation in Omicron clades were deletion in Nucleocapsid, deletion in 3’-untranslated region, and truncation in open reading frame 8.


Subject(s)
12552
18.
BMC Infect Dis ; 22(1): 879, 2022 Nov 22.
Article in English | MEDLINE | ID: covidwho-2139169

ABSTRACT

BACKGROUND: The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies. METHODS: To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle. RESULTS: 180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57-73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61-2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63-2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively. CONCLUSIONS: Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure. Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020.


Subject(s)
COVID-19 , Respiratory Insufficiency , Adult , Male , Humans , Aged , Female , COVID-19/therapy , Standard of Care , Plasma
19.
Am J Respir Cell Mol Biol ; 67(5): 520-527, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2138375

ABSTRACT

Coronavirus disease (COVID-19) begins with upper airway symptoms but proceeds in a significant proportion of patients to life-threatening infection of the lower respiratory tract, where an exuberant inflammatory response, edema, and adverse parenchymal remodeling impair gas exchange. Respiratory failure is caused initially by flooding of the airspaces with plasma exudate, sloughed epithelium, and inflammatory cells. For many patients with COVID-19, this acute phase has been observed to give way to a prolonged course of acute respiratory distress syndrome, and a significant proportion of patients go on to develop fibroproliferative remodeling of the lung parenchyma, which lengthens the duration of respiratory impairment and mechanical ventilation. Monocyte-derived macrophages have previously been implicated in the fibrotic phase of lung injury in multiple models. From several recent studies that used single-cell genomic techniques, a profile of the transcriptomic state of COVID-19 lung macrophages has emerged. Linkages have been made between these macrophages, which are monocyte-derived and CD163+, and profibrotic macrophages found in other contexts, including animal models of fibrosis and idiopathic pulmonary fibrosis. Here, emerging concepts of macrophage profibrotic function in COVID-19 are highlighted with a focus on gaps in knowledge to be addressed by future research.


Subject(s)
COVID-19 , Respiratory Insufficiency , Animals , Transcriptome , Macrophages, Alveolar , Lung
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