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Gastrointestinal (GI) manifestations of the coronavirus disease 2019 (COVID-19) pandemic are frequently observed in SARS-CoV-2-infected individuals at distinct time intervals after the initial diagnosis. Psychological distress in the form of anxiety, burnout, and depression is regarded as a common complication of COVID-19, but also as a risk factor for the development and exacerbation of irritable bowel syndrome (IBS), which is highly prevalent among COVID-19 patients and the general population. The pathophysiological mechanisms culminating in the diagnosis of IBS are yet to be fully understood, however, factors including gut–brain interaction, COVID-19-related intestinal damage, and other external influences might play a role in this process. While long-term GI complications of COVID-19 such as IBS are speculated to develop as a result of a multifaceted interaction between the virus itself with the host, in addition to the effects of psychological distress, further research on this topic is warranted. The purpose of this study was to explore possible factors correlating with the development of IBS and depression during the follow-up period post-COVID-19 infection. © 2023 Journal of Nature and Science of Medicine ;Published by Wolters Kluwer - Medknow.
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Background Understanding health trends and estimating the burden of disease at the national and subnational levels helps policy makers track progress and identify disparities in overall health performance. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides comprehensive estimates for Pakistan. Comparison of health indicators since 1990 provides valuable insights about Pakistan's ability to strengthen its health-care system, reduce inequalities, improve female and child health outcomes, achieve universal health coverage, and meet the UN Sustainable Development Goals. We present estimates of the burden of disease, injuries, and risk factors for Pakistan provinces and territories from 1990 to 2019 based on GBD 2019 to improve health and health outcomes in the country. Methods We used methods and data inputs from GBD 2019 to estimate socio-demographic index, total fertility rate, cause-specific deaths, years of life lost, years lived with disability, disability-adjusted life-years, healthy life expectancy, and risk factors for 286 causes of death and 369 causes of non-fatal health loss in Pakistan and its four provinces and three territories from 1990 to 2019. To generate estimates for Pakistan at the national and subnational levels, we used 68 location-years of data to estimate Pakistan-specific demographic indicators, 316 location-years of data for Pakistan-specific causes of death, 579 location-years of data for Pakistan-specific non-fatal outcomes, 296 location-years of data for Pakistan-specific risk factors, and 3089 location-years of data for Pakistan-specific covariates. Findings Life expectancy for both sexes in Pakistan increased nationally from 61 center dot 1 (95% uncertainty interval [UI] 60 center dot 0-62 center dot 1) years in 1990 to 65 center dot 9 (63 center dot 8-67 center dot 8) years in 2019;however, these gains were not uniform across the provinces and federal territories. Pakistan saw a narrowing of the difference in healthy life expectancy between the sexes from 1990 to 2019, as health gains for women occurred at faster rates than for men. For women, life expectancy increased by 8 center dot 2% (95% UI 6middot3-13middot8) between 1990 and 2019, whereas the male life expectancy increased by 7 center dot 6% (3 center dot 5-11 center dot 8). Neonatal disorders, followed by ischaemic heart disease, stroke, diarrhoeal diseases, and lower respiratory infections were the leading causes of all-age premature mortality in 2019. Child and maternal malnutrition, air pollution, high systolic blood pressure, dietary risks, and tobacco consumption were the leading all-age risk factors for death and disability-adjusted life-years at the national level in 2019. Five non-communicable diseases-ischaemic heart disease, stroke, congenital defects, cirrhosis, and chronic kidney disease-were among the ten leading causes of years of life lost in Pakistan. Burden varied by socio-demographic index. Notably, Balochistan and Khyber Pakhtunkhwa had the lowest observed gains in life expectancy. Dietary iron deficiency was the leading cause of years lived with disability for both men and women in 1990 and 2019. Low birthweight and short gestation and particulate matter pollution were the leading contributors to overall disease burden in both 1990 and 2019 despite moderate improvements, with a 23 center dot 5% (95% UI 3 center dot 8-39 center dot 2) and 27 center dot 6% (14 center dot 3-38 center dot 6) reduction in age-standardised attributable DALY rates during the study period. Interpretation Our study shows that progress has been made on reducing Pakistan's disease burden since 1990, but geographical, age, and sex disparities persist. Equitable investment in the health system, as well as the prioritisation of high-impact policy interventions and programmes, are needed to save lives and improve health outcomes. Pakistan is facing several domestic and foreign challenges-the Taliban's return to power in Afghanistan, political turmoil, catastrophic flooding, the COVID-19 pandemic-that will shape the trajectory of the country's health and development. Pakistan must address the burden of infectious disease and curb rising rates of non-communicable diseases. Prioritising these three areas will enhance Pakistan's ability to achieve universal health coverage, meet its Sustainable Development Goals, and improve the overall health outcomes.
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The mortality of coronavirus disease 2019 (COVID-19) disease is very high among the elderly or individuals having comorbidities such as obesity, cardiovascular diseases, lung infections, hypertension, and/or diabetes. Our study characterizes the metagenomic features in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected patients with or without type 2 diabetes, to identify the microbial interactions associated with its fatal consequences.This study compared the baseline nasopharyngeal microbiome of SARS-CoV-2-infected diabetic and nondiabetic patients with controls adjusted for age and gender. The metagenomics based on next-generation sequencing was performed using Ion GeneStudio S5 Series and the data were analyzed by the Vegan-package in R. All three groups possessed significant bacterial diversity and dissimilarity indexes (p < 0.05). Spearman's correlation coefficient network analysis illustrated 183 significant positive correlations and 13 negative correlations of pathogenic bacteria (r = 0.6-1.0, p < 0.05), and 109 positive correlations between normal flora and probiotic bacteria (r > 0.6, p < 0.05). The SARS-CoV-2 diabetic group exhibited a significant increase in pathogens and secondary infection-causing bacteria (p < 0.05) with a simultaneous decrease of normal flora (p < 0.05). The dysbiosis of the bacterial community might be linked with severe consequences of COVID-19-infected diabetic patients, although a few probiotic strains inhibited numerous pathogens in the same pathological niches. This study suggested that the promotion of normal flora and probiotics through dietary supplementation and excessive inflammation reduction by preventing secondary infections might lead to a better outcome for those comorbid patients.
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Objectives: This study aimed to evaluate the acceptance of the coronavirus vaccine and the attitude of people residing in the southern part of Karachi, Pakistan. Method(s): This web-based cross-sectional research was conducted among the citizens of the southern part of Karachi from Oct to Dec 2021. The survey for the study was adopted and modified from the formerly conducted study by El-Elimat et al, comprising individuals aged more than 18 years of age. Acceptance and predictors of vaccine acceptance were assessed using the Chi-square test and Binary logistic regression. Result(s): The acceptance rate for the coronavirus vaccine was quite high (87%). Males demonstrated a higher acceptance rate. The older aged individuals (>35 years old) also showed higher acceptance when likened to younger participants (OR = 1.84, 95 CI% = 2.893-1.171, p < .008). Individuals not infected with COVID-19 showed less acceptance towards vaccina-tions (OR = 0.431, 95CI% = 0.233- 0.799, p < .008). Similarly, respondents believing the COVID-19 vaccine to be a conspiracy were less likely to show acceptance towards the vaccination process (OR= 0.893, 95 CI% = 0.575-1.387, p= 0. 614). Conclusion(s): Differences in the acceptance rate between males of older age as compared to younger population and females have demonstrated higher acceptance towards vaccination. Sinopharm followed by Sinovac was the most frequently used to provide immunization to the Pakistani population. Copyright © 2022, Khyber Medical College. All rights reserved.
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INTRODUCTION: Previous randomized trials suggest the benefit of inhaled budesonide for COVID-19 patients in outpatient settings. We evaluated available studies on the effect of the therapeutic use of inhaled corticosteroids (ICS) on mortality and pertinent clinical outcomes. METHOD(S): A comprehensive literature search was conducted across the WHO, LitCOVID, and EMBASE databases from inception until June 30th, 2022. The primary outcome was overall mortality and secondary outcomes included symptom-based clinical improvement rates at day 14, ER visits or hospitalization, and adverse events. Data analysis was performed using Review Manager Software, version 5.2, to evaluate the combined odds ratio (OR) with 95% confidence intervals (CI) using a random-effects model. RESULT(S): Nine studies (7 RCTs (3 budesonide, 3 ciclesonide, 1 fluticasone RCTs), & 2 observational studies) were included in the mortality meta-analysis. Of the 3,934 patients included, 103 patients died (44 out of 1925 in the ICS group and 59 out of 2009 in the non-ICS group). The odds of mortality in the therapeutic ICS use group were lower compared to the non-ICS therapy group (OR 0.78, 95% CI 0.48-1.28, p-value=0.33, I2=0%). The result was statistically insignificant, possibly due to the low mortality rate. But therapeutic ICS showed statistically significant clinical improvement rates at day 14 (5 RCTs;3 Ciclesonide, 2 Budesonide) (OR 1.56, 95% CI 1.31-1.86, p < 0.0001, I2=0%). The number of ED visits/Hospitalization rate, and adverse events were not statistically significant between the groups (OR 0.73, 95% CI 0.32-1.70, p= 0.47 I2=75% and OR 1.10 95% CI 0.67-1.82, p=0.70, I2=28%). CONCLUSION(S): This meta-analysis shows that the therapeutic use of ICS in COVID-19 is associated with higher symptom-based clinical improvement rates. Although the reduction in mortality odds remained insignificant, as the overall mortality rates were low which increased the confidence interval overall. Early administration of ICS showed a trend towards the reduced likelihood of urgent care needs. Well-designed trials are needed to explore ICS efficacy in patients with a high risk of disease progression and in reducing the incidence of long-term COVID-19 symptoms or post-acute sequelae of SARS-CoV-2.
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INTRODUCTION: Studies of hospitalized patients with COVID-19 have found varying clinical outcomes associated with underlying respiratory conditions and inhaled corticosteroid use. We performed a systematic review to summarize the effect of the pre-hospital use of inhaled corticosteroids on the clinical outcomes in patients with COVID-19. METHOD(S): A comprehensive literature accrual was conducted across the WHO, CDC, and LitCovid PubMed COVID-19 databases from inception until June 30th, 2022. The Overall mortality was the primary outcome, and the secondary outcomes were the need for intensive care unit (ICU) admission and the need for invasive mechanical ventilation (IMV). All included studies were observational and reported the desired outcomes with pre-hospital use of ICS in COVID-19 patients. Data analysis was performed using Review Manager Software, version 5.2 to evaluate the combined odds ratio (OR) with respective 95% confidence intervals (CI) using a random-effects model. RESULT(S): Nineteen studies assessed mortality and were included in the meta-analysis. A total of 1,122,329 patients were included, of which 10,466 patients died (2,289 out of 824,005 in ICS arm patients and 8,177 out of 298,324 in the non-ICS arm), resulting in the unadjusted odds of death (OR 1.36, 95% CI 1.09-1.70, I2=82%). However, In the subgroups analyses of COPD patients (8 studies;598 out of 106,659 in the ICS arm and 353 out of 44,496 in the non-ICS arm) and Asthma patients (7 studies;705 out of 714,126 in the ICS arm and 179 out of 222,577 in the non-ICS arm), significantly increased risk of death was not shown (OR 1.20, 95% CI 0.93-1.57, I2=32%, OR 1.61, 95% CI 0.97-2.66, I2=82% respectively). There were no significantly increased odds in the assessed secondary outcomes;ICU admission (13 studies, OR 1.11, 95% CI 0.82-1.51, I2=84%), need for mechanical ventilation (7 studies, OR 1.21, 95% CI 1.00-1.45, I2=0%). CONCLUSION(S): Prehospital use of ICS in COVID-19 patients is associated with higher odds of overall mortality in unadjusted analysis. However, this was not shown in the subgroup of patients with a history of COPD or Asthma. Other clinical outcomes such as the need for ICU admission and mechanical ventilation show similar trends. Future research with well-designed clinical trials is needed to validate our findings.
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INTRODUCTION: The reduction of mortality in COVID-19 has been clinically established only for Dexamethasone and Tocilizumab to date, but the overall mortality in COVID-19 remains high. Baricitinib is a Janus Kinase 1/2 Inhibitor with known anti-inflammatory and anti-viral properties. The US FDA recently approved Baricitinib for the treatment of hospitalized adults with COVID-19 requiring either supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). We performed a meta-analysis of Randomized Controlled Trials (RCT) and observational studies assessing the effect of Baricitinib on mortality outcomes in hospitalized patients with COVID-19. METHOD(S): A systematic literature search was conducted on electronic databases including NIH LitCovid, WHO COVID-19 database, EMBASE, and Cochrane Central from inception until June 30th, 2022. Randomized Controlled Trials and observational studies evaluating the efficacy of Baricitinib in hospitalized patients with COVID-19 were screened for the assessment of all-cause mortality as the outcome. RESULT(S): Twenty-three studies (18 observational and 5 RCTs) were included in the mortality meta-analysis. Of the 16,390 patients (4,565 observational, 11,825 RCTs), 2,139 patients died (903 out of 7,610 in the Baricitinib arm and 1,236 out of 8,780 in the non-Baricitinib arm). Using the random-effects model, the odds of mortality in the therapeutic Baricitinib use showed a statistically significant reduction in all-cause mortality in hospitalized COVID-19 patients (OR 0.67, 95% CI 0.50-0.90;p=0.008, I2=79%). A similar trend of decreased mortality was observed in the subgroup analysis by study design (Observational OR 0.59, 95% CI 0.35-0.97, p=0.04, I2=83%;RCTs OR 0.72, 95% CI 0.56-0.93, p=0.01, I2=53%). CONCLUSION(S): Baricitinib used along with the standard of care treatments is associated with a reduction in mortality in hospitalized patients with COVID-19 disease.
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INTRODUCTION: Coagulopathy and thromboembolic events are poor prognostic indicators of COVID-19 disease. There is a discrepancy in the results of different studies regarding the effects of chronic anticoagulation on clinical outcomes. This systematic review aims to summarize the evidence on the impact of chronic anticoagulation on clinical outcomes in COVID-19. METHOD(S): A Literature search was performed on LitCovid PubMed, WHO, and Embase databases from inception (December 2019) till May 2022. Our eligibility criteria included original studies that reported the association between prior use of anticoagulants for unrelated indications at the time of COVID-19 diagnosis and the patient outcomes in adults suffering from COVID-19. The risk of thromboembolic events in COVID-19 infected patients on chronic anticoagulation is the primary outcome and severity of COVID-19 disease in terms of ICU admission or invasive mechanical ventilation/intubation requirements, and all-cause mortality were the secondary outcomes. Random effects models were used to compute crude ODDs ratios (OR) and adjusted odds ratios (aOR) with 95% confidence intervals (CIs). RESULT(S): A total of 44 observational studies met our inclusion criteria. In unadjusted analysis, prior anticoagulation was not associated with reduced risk of thromboembolic events in COVID-19 patients (N=43851, 9 studies, OR 0.67 [0.22, 2.07];p= 0.49;I2= 95%). However, pre-hospital use of anticoagulants significantly increase the risk of allcause mortality in COVID-19 patients (N= 580601;37 studies, OR 1.56 [1.22, 2.01];p=0.0005;I2= 97%). There was no statistically significant association between prehospital anticoagulants usage and COVID-19 disease severity (N=186239;20 studies, OR 0.96 [0.70, 1.33];p= 0.82;I2= 88%). Pooling adjusted estimates revealed no statistically significant association between pre-hospital use of anticoagulants and risk of Thromboembolic events in COVID-19 patients (aOR= 0.85 [0.34, 2.12];p= 0.72), COVID-19 related mortality (aOR= 0.93 [0.82, 1.07];p= 0.32), and the severity of COVID-19 infection (aOR= 0.96 [0.72, 1.30];p= 0.81). CONCLUSION(S): Prehospital use of anticoagulation was not significantly associated with reduced risk of thromboembolic events, improved survival, and lower severity of disease in COVID-19 patients.
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This study was conducted during the COVID-19 pandemic to explore whether team-based, online learning activities play a role in enhancing undergraduate engineering students' critical thinking skills. To conduct the study, we distributed a Google Form-based online survey among undergraduate engineering students through Tecnolo & PRIME;gico de Monterrey learning management system platform during the fall semester of 2020. In total, we received 50 complete responses through a convenient sampling approach. To analyze the quantitative data, we applied a hierarchical regression technique using the IBM SPSS 26.0 statistical software program. The findings of this study affirm that participation in team-based online learning activities meant to improve (1) the quality of learning and (2) reasoning ability have a significant positive correlation with critical thinking skills of undergraduate students in engineering programs. We also conclude that quality of learning has higher significant association with critical thinking skills as compared to reasoning ability
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Objective COVID-19 resulted in dentistry being declared high-risk occupation due to the mode of the spread of the virus. This resulted in partial and complete closure of dental practices around the world, reducing revenue of practitioners. Hence, study aims to evaluate financial impact on dental practitioners in Pakistan and UAE. Materials and Methods A questionnaire-based cross-sectional study was conducted from July 2020 to January 2021. It involved questions relating to demographics and financial challenges faced, associated with change in standard operating procedures due to pandemic. The descriptive statistics were expressed as frequency and percentage. Statistical analysis was performed by Chi-square test or Fischer's exact test. Results In total, 427 respondents participated in the study. Approximately half (55.7%) of the respondents had their practices shut down, while 89.9% observed decrease in patient flow. The majority (82.2%) of respondents had to buy personal protective equipment (PPE), whereas 66.7% had to pay a high cost for that. Almost 87.3% of respondents reported having experienced financial constraints because of the pandemic related changes to the practice. Moreover, 27.8% reported staff being laid off, which were mostly due to monetary constrictions. Conclusion Dental professionals faced a considerable impact on their practice and financial situation due to pandemic. Policies must be made to support such professionals in times of emergency who are at higher risk of being most affected with respect to health and finances. © 2022 Wolters Kluwer Medknow Publications. All rights reserved.
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This study aims to investigate the health-related quality of life and coping strategies among COVID-19 survivors in Bangladesh. Methods: This is a cross-sectional study of 2198 adult, male was 72.38% (n=1591) and female 27.6% (n=607), COVID-19 survivors living in Bangladesh. Data were collected from previously diagnosed COVID-19 participants (confirmed by an RT-PCR test) via door-to-door interviews in the eight different divisions in Bangladesh. For data collection, Bengali translated Brief COPE inventory and WHO Brief Quality of Life (WHO-QOLBREF) questionnaires were used. The data collection period was from June 2020 to March 2021. Results: Males 72.38% (1591) were more affected by COVID-19 than females 27.62% (607). Age showed significant correlations with physical, psychological and social relationships; whereas, gender showed only significant correlation with physical health (p<0.001). Marital status, occupation, living area, and co-morbidities showed significant co-relation with all four domains of QoL (p<0.001). Education and affected family members showed significant correlation with physical and social relationship (p<0.001). However, smoking habit showed significant correlations with both social relationship and environment (p<0.001). Age and marital status showed a significant correlation with avoidant coping strategy (p<0.001); whereas gender and co-morbidities showed significant correlation with problem focused coping strategies (p<0.001). Educational qualification, occupation and living area showed significant correlation with all three coping strategies (p<0.001). Conclusion: Survivors of COVID-19 showed mixed types of coping strategies; however, the predominant coping strategy was avoidant coping, followed by problem focused coping, with emotion focused coping reported as the least prevalent. Marital status, occupation, living area and co-morbidities showed a greater effect on QoL in all participants.
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COVID-19 , Sexual Dysfunctions, PsychologicalABSTRACT
Coronavirus Disease 2019 caused by the Severe Acute Respiratory Syndrome Coronavirus 2 has completely crippled the health and economic sectors across the globe and turned out to be a major threat to human population. The potential role of virus has been considered as an originating cause of tissue injury by disrupting the renin-angiotensin system. However, hyperactive function of immune system also leads to inexorable tissue injury through cytokine storms. Therefore, improved therapeutic interventions have been devised by modulation of the response of immune system. Apart from current ongoing treatments efficacy and safety profile is still a big challenge. MSCs mostly isolated from human bone marrow (BM), in addition to umbilical cord (UC) and adipose tissue (AT) has a great potential for multi-potential differentiation and self-renewal. This manuscript aims to summarize the potential therapeutic applications of stem cell derived therapy with biomedical application in terms of immune-mediated pathophysiological conditions with associated challenges and future advancement.
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Background: The risk of transmission of novel SARS CoronaVirus-2 among health care workers can be reduced using personal protective equipment. It is critical to follow guidelines for appropriate use of protective gear to avoid its wastage. This study aimed to evaluate frontline healthcare workers' understanding of effective donning and doffing of protective equipment in the wake of recent emergence of corona virus disease.Physical impacts due to its prolonged usage were also identified. Material and Methods: A cross sectional survey was conducted targeting frontline health care workers from June till July 2021. Data was analyzed using SPSS version 24. Descriptive analysis was performed for qualitative variables.Chi-square test was utilized to determine association between qualitative variables and p <0.05 was considered to be statistically significant. Results: A total of 204 responses were received. Surgical masks (53.9%), gloves (51.5%), gowns (46.1%) and N95 respirator (40.7%) were most frequently used. Physicians had better knowledge on correct utilization of protective equipment as compared to non-physicians, p<0.001.Only 55.9% and 47.1% participants knew correct donning and doffing sequence respectively.The most prevalent mistakes while doffingwere touching front of mask and potentially contaminated surfaces followed by incorrect doffing sequence.Mostrespondentsmentioned scarcity of protective gear. Around 53% participants did not attend any training session on utilization of personal protective equipment. Prolonged exposure to masks and gloves led to acne, facial marks and itching. Frequent practice of hand hygiene was linked with skin dryness and cracking, p<0.001. Conclusion: We observed lack of expertise in donning and doffing technique. Mostly mistakes occurred during doffing, so interactive workshops are required to train health care workers.Most common dermatological manifestationsdue to use of masks and gloves included acne, facial markings, and itching. Adverse effects of prolonged use of PPE can be avoided by having shorter duration of working hours and giving rest during the shifts.
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Background: Giant cell arteritis (GCA) is a systemic vasculitis affecting large to medium-sized vessels. Cranial nerve lesions are frequently documented secondary to GCA, however peripheral nerves are rarely involved. Objectives: We present an unusual case of a GCA-associated isolated high median nerve palsy. Methods: Case report. Results: A 76 year old white British female presented in Spain with three weeks of frontotemporal headaches, mandibular claudication, photopsia and constitutional symptoms, followed by acute-onset right hand paresis and dysaesthesia. Acute-phase reactants were elevated. COVID-19 PCR was negative. Shortly after admission she developed acute bilateral anterior ischaemic optic neuropathy and tongue necrosis with autoamputation. Temporal artery ultrasound and biopsy confirmed GCA. PET-CT showed no evidence of a diffuse large-vessel vasculitis. She was repatriated to the UK for ongoing inpatient care. Upper limb neurophysiology two months later demonstrated an isolated right high median nerve lesion, with reduced median motor responses and absent sensory responses with denervation in extensor carpi radialis. Imaging excluded a central lesion. The timing of her symptoms suggested the lesion was secondary to GCA. Treatment was with tocilizumab, methotrexate and tapering corticosteroids, alongside PEG feeding and careful multi-disciplinary rehabilitation. Conclusion: We suggest there are two important learning points from this complex case. Firstly, peripheral nerve lesions can occur in GCA, although they are rare. A literature search identified a modest number of case reports of brachial plexus or lower cervical nerve lesions1,2. Neurologic manifestations in GCA are attributed to vasculitis of the vasa nervorum, or extension of inflammation from arteries to contiguous nerves1,2. The restriction of clinical involvement to the median nerve alone would appear to favour the former mechanism. Functional recovery of neurological deficits is typically partial at best. Secondly, this case highlights the difficulty faced by clinicians in recognising GCA and the importance of urgent treatment with glucocorticoids. The patient developed GCA during the ongoing COVID-19 pandemic when Spain was the second-worst affected European country (5% seroprevalence;95% CI 4.7-5.4)3. The partial overlap in symptoms between GCA and COVID-19 (e.g. headache, pyrexia, malaise, elevated acute-phase reactants) can cause diagnostic confusion and treatment delay4. GCA should be considered in the differential diagnosis of older patients with suspected COVID-19, or the non-specifically unwell elderly patient.
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Based on transmissibility and high mortality rate of COVID-19, it has incapacitated the global health care systems and economy. The emergence of 2019 novel coronavirus (2019-nCoV) outbreak has put the global population under major life-threatening state. The global expeditious spread of COVID-19 pandemic from China is mainly based on airborne transmission of aerosols and possibly through viral droplets due to close contact with infected individuals especially during speaking, sneezing and breathing. Based on clinical requirements dental practitioners and patients are under considerable huge risk of exposure to SARS-CoV-2 infection. Compared to other healthcare professions, the epidemic period of COVID-19 has posed severe limitations in terms of diagnosis and treatment of oral health emergencies due to lack of instructional guidelines, swift and contagious spread of virus presenting devastating situation of cure and prevention. The aim of this article is to share the general perspective and associated challenges of post pandemic impact from dental practitioners, clinicians and faculty affiliated to dental education and clinical dentistry practice across the globe due to coronavirus disease (COVID-19) outbreak. In this article we will focus on our recent understanding related to the prevalence, viral biological characteristic, and mode of transmission and clinical manifestation of SARS-CoV-2. The potential risk of transmission among dental setup emphasizes the implementation of effective strategies and policies to mitigate the transmission rate and impact of SARS-CoV-2.
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Background: SARS-CoV-2 is continuously spreading worldwide at an unprecedented scale and evolved into seven clades according to GISAID where four (G, GH, GR and GV) are globally prevalent in 2020. These major predominant clades of SARS-CoV-2 are continuously increasing COVID-19 cases worldwide; however, after an early rise in 2020, the death-case ratio has been decreasing to a plateau. G clade viruses contain four co-occurring mutations in their genome (C241T+C3037T+C14408T: RdRp.P323L+A23403G:spike.D614G). GR, GH, and GV strains are defined by the presence of these four mutations in addition to the clade-featured mutation in GGG28881-28883AAC:N. RG203-204KR, G25563T:ORF3a.Q57H, and C22227T:spike.A222V+C28932T-N.A220V+G29645T, respectively. The research works are broadly focused on the spike protein mutations that have direct roles in receptor binding, antigenicity, thus viral transmission and replication fitness. However, mutations in other proteins might also have effects on viral pathogenicity and transmissibility. How the clade-featured mutations are linked with viral evolution in this pandemic through gearing their fitness and virulence is the main question of this study. Methodology: We thus proposed a hypothetical model, combining a statistical and structural bioinformatics approach, endeavors to explain this infection paradox by describing the epistatic effects of the clade-featured co-occurring mutations on viral fitness and virulence. Results and Discussion: The G and GR/GV clade strains represent a significant positive and negative association, respectively, with the death-case ratio (incidence rate ratio or IRR = 1.03, p <0.001 and IRR= 0.99/0.97, p < 0.001), whereas GH clade strains showed no association with the Docking analysis showed the higher infectiousness of a spike mutant through more favorable binding of G614 with the elastase-2. RdRp mutation p.P323L significantly increased genome-wide mutations (p<0.0001) since more expandable RdRp (mutant)-NSP8 interaction may accelerate replication. Superior RNA stability and structural variation at NSP3:C241T might impact upon protein or RNA interactions. Another silent 5'UTR:C241T mutation might affect translational efficiency and viral packaging. These G-featured co-occurring mutations might increase the viral load, alter immune responses in host and hence can modulate intra-host genomic plasticity. An additional viroporin ORF3a:p.Q57H mutation, forming GH-clade, prevents ion permeability by cysteine (C81)-histidine (H57) inter-transmembrane-domain interaction mediated tighter constriction of the channel pore and possibly reduces viral release and immune response. GR strains, four G clade mutations and N:p.RG203-204KR, would have stabilized RNA interaction by more flexible and hypo-phosphorylated SR-rich region. GV strains seemingly gained the evolutionary advantage of superspreading event through confounder factors; nevertheless, N:p.A220V might affect RNA binding. Conclusion: These hypotheses need further retrospective and prospective studies to understand detailed molecular and evolutionary events featuring the fitness and virulence of SARS-CoV-2.