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2.
Life (Basel) ; 12(7)2022 Jul 21.
Article in English | MEDLINE | ID: covidwho-1957380

ABSTRACT

Healthcare systems have been under immense pressure since the beginning of the COVID-19 pandemic; hence, studies on using machine learning (ML) methods for classifying ICU admissions and resource allocation are urgently needed. We investigated whether ML can propose a useful classification model for predicting the ICU admissions of COVID-19 patients. In this retrospective study, the clinical characteristics and laboratory findings of 100 patients with laboratory-confirmed COVID-19 tests were retrieved between May 2020 and January 2021. Based on patients' demographic and clinical data, we analyzed the capability of the proposed weighted radial kernel support vector machine (SVM), coupled with (RFE). The proposed method is compared with other reference methods such as linear discriminant analysis (LDA) and kernel-based SVM variants including the linear, polynomial, and radial kernels coupled with REF for predicting ICU admissions of COVID-19 patients. An initial performance assessment indicated that the SVM with weighted radial kernels coupled with REF outperformed the other classification methods in discriminating between ICU and non-ICU admissions in COVID-19 patients. Furthermore, applying the Recursive Feature Elimination (RFE) with weighted radial kernel SVM identified a significant set of variables that can predict and statistically distinguish ICU from non-ICU COVID-19 patients. The patients' weight, PCR Ct Value, CCL19, INF-ß, BLC, INR, PT, PTT, CKMB, HB, platelets, RBC, urea, creatinine and albumin results were found to be the significant predicting features. We believe that weighted radial kernel SVM can be used as an assisting ML approach to guide hospital decision makers in resource allocation and mobilization between intensive care and isolation units. We model the data retrospectively on a selected subset of patient-derived variables based on previous knowledge of ICU admission and this needs to be trained in order to forecast prospectively.

3.
BMC Sports Sci Med Rehabil ; 14(1): 74, 2022 Apr 20.
Article in English | MEDLINE | ID: covidwho-1896375

ABSTRACT

BACKGROUND: Current evidence still emerging regarding the risk of cardiovascular (CV) sequel associated with coronavirus disease 2019 (COVID-19) infection, and considerable replicated studies are needed to ensure safe return-to-play. Therefore, we aimed in this systematic review to measure the prevalence of CV complications suffered by COVID-19 athletic patients, explore the outcomes, optimal approaches to diagnoses, and safe return-to-play considerations. METHODS: A systematic search on post COVID-19 infection quantitative studies among athletes was conducted following MeSH terms in Medline, Cochrane Library, Ovid, Embase and Scopus (through 15 January 2022). We included peer-reviewed studies reported athletes' CV complications and the outcomes post COVID-19 infection. Editorials, letters, commentaries, and clinical guidelines, as well as duplicate studies were excluded. Studies involving non-athletic patients were also excluded. Quality assessment was performed using Newcastle-Ottawa Scale. RESULTS: We included 15 eligible articles with a total of 6229 athletes, of whom 1023 were elite or professional athletes. The prevalence of myocarditis ranged between 0.4% and 15.4%, pericarditis 0.06% and 2.2%, and pericardial effusion between 0.27% and 58%. Five studies reported elevated troponin levels (0.9-6.9%). CONCLUSIONS: This study provides a low prevalence of CV complications secondary to COVID-19 infection in short-term follow-up. Early recognition and continuous assessment of cardiac abnormality in competitive athletes are imperative to prevent cardiac complications. Establishing a stepwise evaluation approach is critical with an emphasis on imaging techniques for proper diagnosis and risk assessment for a safe return to play.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-310273

ABSTRACT

Nowadays, the human population is facing the third and may be the worst pandemic caused by human coronaviruses (CoVs). The virus was first reported in Wuhan, China on 31 December 2019 and spread within short time to almost all countries of the world. Genome analysis of the early virus isolates has revealed high similarity with SARS-CoV and hence the new virus was officially named SARS-CoV-2. Since CoVs have the largest genome among all RNA viruses, they can adapt many point mutation and recombination events;particularly in spike gene, that enable these viruses to rapidly change and evolve in nature. CoVs are known to cross the species boundaries by using different cellular receptors. SARS-CoV-2 is believed to originate in bats and transmitted to human being through an ill-defined intermediate host. In the current review, different aspects of SARS-CoV-2 biology and pathogenicity are discussed including virus genetics and evolution, spike protein and its role in evolution and adaptation to novel hosts, and virus transmission and persistence in nature. In addition, the immune response developed during SARS-CoV-2 infection is demonstrated with special reference to the interplay between immune cells and their role in disease progression. We believe that SARS-CoV-2 outbreak will not be the last and spillover of CoVs from bats will continue. Therefore, establishing intervention approaches to reduce the likelihood of future CoVs spillover from the natural reservoirs is a priority.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-305398

ABSTRACT

The uncertainty about COVID-19 outcomes in angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) users continues with contradictory findings. The aim of this study was to determine the effect of ACEI/ARB use in patients with severe COVID-19. This retrospective cohort study done in two Saudi public specialty hospitals designated as COVID-19 referral facilities. We included 354 patients with confirmed diagnosis of COVID-19 between April and June 2020, of which 146 were ACEI/ARB users and 208 were non-ACEI/ARB users. Controlling for confounders, we conducted a multivariate logistic regression and a sensitivity analysis using propensity score matched (PSM) patients. Compared to non-ACEI/ARB users, ACEI/ARB users had an eight-fold higher risk of developing critical or severe COVID-19 (OR=8.25, 95%CI=3.32-20.53);a nearly 7-fold higher risk of intensive care unit (ICU) admission (OR=6.76, 95%CI=2.88-15.89) and a nearly 5-fold higher risk of requiring noninvasive ventilation (OR=4.77,95%CI=2.15-10.55). Patients with diabetes, hypertension, and/or renal disease had a five-fold higher risk of severe COVID-19 disease (OR=5.40,95%CI=2.0-14.54]. These results were confirmed in the PSM analysis. In general, but especially among patients with hypertension, diabetes, and/or renal disease, ACEI/ARB use is associated with a significantly higher risk of severe or critical COVID-19 disease, and ICU care.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-305380

ABSTRACT

Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China in December 2019 has led to a pandemic. Influenza and coronaviruses are known to show cross-reactive immunity. Therefore, we hypothesized that influenza vaccination may provide a protective effect against SARS-CoV-2.Methods: We investigated the presence of SARS-CoV-2 in flu vaccinated and unvaccinated ILI cases by real time PCR, followed by confirmation of evolutionary and spatial relationships using next generation sequencing (NGS).Results: Out of 739 nasopharyngeal specimens collected from November 2019 to March 2020, we found 37 samples were positive for SARS-CoV-2 RNA mostly during February 2020. We observed that the overall incidence of ILI cases during 2019-2020 influenza season was considerably higher than previous years and was gradually replaced with SARS-CoV-2 which indicated a slow transmission among ambulatory patients. NGS data confirmed independent introductions and transmission earlier than previously thought. Phylogenetic reconstruction of representative isolates showed clustering in the GH clade which is characterized by two amino acid changes in spike gene (D614G) and NS3 (Q57H). Shortness of breath was significantly lower (p = 0.04) in the ILI cases with the history of influenza vaccination suggesting a protective effect of the influenza vaccine, at least in part, on COVID-19 disease outcomes.Conclusions: The detection of SARS-CoV-2 among ILI patients shows the importance of flu vaccination and ILI surveillance system and warrants their further strengthening to mitigate the ongoing transmission of SARS-CoV-2 and to guide policy makers to optimize public health interventions.Funding Statement: This work was supported by the Research Center at King Fahad Medical city (Grant No 20- 066).Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Ethics Approval Statement: The study was approved by the Institutional Review Board at King Fahad Medical City (IRB Log No. 19-477 approved on 25 September 2019) for influenza vaccine effectiveness study, started from 7 November 2019. When COVID-19 pandemic started, the collection of samples stopped on the 2nd of March 2020. To screen those samples for SARS-CoV-2, we applied for another IRB (Log No. 20-161 approved on 23 March 2020).

7.
Case Rep Psychiatry ; 2021: 3794019, 2021.
Article in English | MEDLINE | ID: covidwho-1591105

ABSTRACT

Besides respiratory symptoms, COVID-19 disease has a wide range of clinical, subclinical, and atypical presentations reported previously. Here, we report the case report of a middle-aged man, with no previous known medical illness, who presented with a 5-day-history of anxiety, fever, confusion, and hallucinations. Patient's SARS-CoV-2 polymerase chain reaction test was positive, and he underwent daily vital signs and respiratory, cardiovascular, and abdominal examinations. Chest radiography, electrocardiogram, microbial culture, biochemistry, and toxicology tests were also investigated. In this report, a case of COVID-19 is described with an unusual presentation of confusion and hallucinations in the absence of severe upper respiratory or constitutional symptoms. The earlier recognition of atypical manifestation, the safer the practice, with optimal timely diagnosis, and less anticipated outbreaks in healthcare facilities. Further studies are needed to establish the underlying pathophysiological mechanisms involved.

8.
mSphere ; 6(4): e0021921, 2021 08 25.
Article in English | MEDLINE | ID: covidwho-1319381

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic infection that emerged in the Middle East in 2012. Symptoms range from mild to severe and include both respiratory and gastrointestinal illnesses. The virus is mainly present in camel populations with occasional zoonotic spill over into humans. The severity of infection in humans is influenced by numerous factors, and similar to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underlying health complications can play a major role. Currently, MERS-CoV and SARS-CoV-2 are coincident in the Middle East and thus a rapid way of sequencing MERS-CoV to derive genotype information for molecular epidemiology is needed. Additionally, complicating factors in MERS-CoV infections are coinfections that require clinical management. The ability to rapidly characterize these infections would be advantageous. To rapidly sequence MERS-CoV, an amplicon-based approach was developed and coupled to Oxford Nanopore long read length sequencing. This and a metagenomic approach were evaluated with clinical samples from patients with MERS. The data illustrated that whole-genome or near-whole-genome information on MERS-CoV could be rapidly obtained. This approach provided data on both consensus genomes and the presence of minor variants, including deletion mutants. The metagenomic analysis provided information of the background microbiome. The advantage of this approach is that insertions and deletions can be identified, which are the major drivers of genotype change in coronaviruses. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in late 2012 in Saudi Arabia. The virus is a serious threat to people not only in the Middle East but also in the world and has been detected in over 27 countries. MERS-CoV is spreading in the Middle East and neighboring countries, and approximately 35% of reported patients with this virus have died. This is the most severe coronavirus infection so far described. Saudi Arabia is a destination for many millions of people in the world who visit for religious purposes (Umrah and Hajj), and so it is a very vulnerable area, which imposes unique challenges for effective control of this epidemic. The significance of our study is that clinical samples from patients with MERS were used for rapid in-depth sequencing and metagenomic analysis using long read length sequencing.


Subject(s)
Coronavirus Infections/virology , Microbiota/genetics , Middle East Respiratory Syndrome Coronavirus/genetics , Aged , Animals , COVID-19/virology , Female , Humans , Male , Middle Aged , SARS-CoV-2/genetics
9.
Front Immunol ; 12: 668725, 2021.
Article in English | MEDLINE | ID: covidwho-1317223

ABSTRACT

COVID-19 severity due to innate immunity dysregulation accounts for prolonged hospitalization, critical complications, and mortality. Severe SARS-CoV-2 infections involve the complement pathway activation for cytokine storm development. Nevertheless, the role of complement in COVID-19 immunopathology, complement-modulating treatment strategies against COVID-19, and the complement and SARS-CoV-2 interaction with clinical disease outcomes remain elusive. This study investigated the potential changes in complement signaling, and the associated inflammatory mediators, in mild-to-critical COVID-19 patients and their clinical outcomes. A total of 53 patients infected with SARS-CoV-2 were enrolled in the study (26 critical and 27 mild cases), and additional 18 healthy control patients were also included. Complement proteins and inflammatory cytokines and chemokines were measured in the sera of patients with COVID-19 as well as healthy controls by specific enzyme-linked immunosorbent assay. C3a, C5a, and factor P (properdin), as well as interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, and IgM antibody levels, were higher in critical COVID-19 patients compared to mild COVID-19 patients. Additionally, compared to the mild COVID-19 patients, factor I and C4-BP levels were significantly decreased in the critical COVID-19 patients. Meanwhile, RANTES levels were significantly higher in the mild patients compared to critical patients. Furthermore, the critical COVID-19 intra-group analysis showed significantly higher C5a, C3a, and factor P levels in the critical COVID-19 non-survival group than in the survival group. Additionally, IL-1ß, IL-6, and IL-8 were significantly upregulated in the critical COVID-19 non-survival group compared to the survival group. Finally, C5a, C3a, factor P, and serum IL-1ß, IL-6, and IL-8 levels positively correlated with critical COVID-19 in-hospital deaths. These findings highlight the potential prognostic utility of the complement system for predicting COVID-19 severity and mortality while suggesting that complement anaphylatoxins and inflammatory cytokines are potential treatment targets against COVID-19.


Subject(s)
Anaphylatoxins/analysis , COVID-19/blood , COVID-19/mortality , Chemokines/blood , Hospital Mortality , SARS-CoV-2/genetics , Severity of Illness Index , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/virology , Case-Control Studies , Cytokine Release Syndrome , Female , Humans , Male , Middle Aged , Prognosis , Young Adult
10.
J Clin Immunol ; 41(7): 1607-1620, 2021 10.
Article in English | MEDLINE | ID: covidwho-1298388

ABSTRACT

The complement system, a network of highly-regulated proteins, represents a vital part of the innate immune response. Over-activation of the complement system plays an important role in inflammation, tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement-modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including seven complement proteins, complement regulatory factors, IL-8, and RANTES in MERS-CoV infected patients without underlying chronic medical conditions. Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a, and C3a was positively correlated with IL-8, RANTES, and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P, suggesting positive regulation of the complement during MERS-CoV infection. High levels of lung C5a, C3a, factor P, IL-8, and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8, and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the prediction of functional partners (proteins) of highly expressed proteins (C5a, C3a, factor P, IL-8, and RANTES), the computational protein-protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified.


Subject(s)
Chemokine CCL5/genetics , Chemokine CCL5/metabolism , Complement C3a/metabolism , Complement C5a/metabolism , Coronavirus Infections/diagnosis , Interleukin-8/metabolism , Lung/metabolism , Middle East Respiratory Syndrome Coronavirus/physiology , Aged , Biomarkers/metabolism , Complement C3a/genetics , Complement C5a/genetics , Coronavirus Infections/metabolism , Coronavirus Infections/mortality , Female , Humans , Interleukin-8/genetics , Male , Middle Aged , Prognosis , Severity of Illness Index , Survival Analysis , Up-Regulation
11.
J Infect Public Health ; 14(8): 994-1000, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1275493

ABSTRACT

BACKGROUND: The new coronavirus disease (COVID-19) has caused more than 1.8 million deaths, with a fatality rate of 2.5% in more than 200 countries as of January 4, 2021. Analysis of COVID-19 clinical features can help predict disease severity and risk of mortality, early identification of high-risk patients, and provide knowledge to inform clinical interventions. OBJECTIVE: The purpose of this study is to investigate the clinical characteristics and possible predictors associated with mortality in patients with COVID-19 admitted to King Fahad (KFH), Ohood, and Miqat hospitals in Madina, Saudi Arabia. METHODS: This retrospective observational study to investigate the clinical characteristic and possible predictors associated with mortality for those 119 mild, moderate, or critically ill patients confirmed by laboratory results to have COVID-19 who were admitted to three hospitals in Madina, Saudi Arabia, from March 25, 2020, to July 30, 2020. Data were collected from December 1, 2020, to December 14, 2020. RESULTS: Of the 119 patients included in the study, the mean age was 54.2 (±15.7) years, with 78.2% survivors and 21.8% non-survivors. The demographic analysis indicated that the likelihood of mortality for patients in the older age group (i.e., ≥65 years) was five times higher than those in the younger age group (OR = 5.34, 95% CI 1.71-16.68, p = 0.004). The results also indicated those patients who admitted to the intensive care unit (ICU) was approximately seven times higher odds of mortality compare with those who were not admitted (OR = 6.48, 95% CI 2.52-16.63, p < 0.001). In addition, six laboratory parameters were positively associated with the odds of mortality: white blood cell count (OR = 1.11, 95% CI 1.02-1.21, p = 0.018), neutrophil (OR = 1.11, 95% CI 1.02-1.22, p = 0.020), creatine kinase myocardial band (OR = 1.02, 95% CI 1.00-1.03, p = 0.030), C-reactive protein (OR = 1.01, 95% CI 1.00-1.01, p = 0.002), urea (OR = 1.06, 95% CI 1.01-1.11, p = 0.026), and lactate dehydrogenase (OR = 1.00, 95% CI 1.00-1.01, p = 0.020). CONCLUSIONS: In this cohort, COVID-19 patients within the older age group (≥65 years) admitted to the ICU with increased C-reactive protein levels in particular, were associated with increased odds of mortality. Further clinical observations are warranted to support these findings and enhance the mapping and control of this pandemic.


Subject(s)
COVID-19 , Aged , Humans , Intensive Care Units , Middle Aged , Pandemics , Retrospective Studies , SARS-CoV-2 , Saudi Arabia/epidemiology
12.
Virol J ; 18(1): 127, 2021 06 14.
Article in English | MEDLINE | ID: covidwho-1269882

ABSTRACT

BACKGROUND: In COVID-19 patients, undetected co-infections may have severe clinical implications associated with increased hospitalization, varied treatment approaches and mortality. Therefore, we investigated the implications of viral and bacterial co-infection in COVID-19 clinical outcomes. METHODS: Nasopharyngeal samples were obtained from 48 COVID-19 patients (29% ICU and 71% non-ICU) and screened for the presence of 24 respiratory pathogens using six multiplex PCR panels. RESULTS: We found evidence of co-infection in 34 COVID-19 patients (71%). Influenza A H1N1 (n = 17), Chlamydia pneumoniae (n = 13) and human adenovirus (n = 10) were the most commonly detected pathogens. Viral co-infection was associated with increased ICU admission (r = 0.1) and higher mortality (OR 1.78, CI = 0.38-8.28) compared to bacterial co-infections (OR 0.44, CI = 0.08-2.45). Two thirds of COVID-19 critically ill patients who died, had a co-infection; and Influenza A H1N1 was the only pathogen for which a direct relationship with mortality was seen (r = 0.2). CONCLUSIONS: Our study highlights the importance of screening for co-infecting viruses in COVID-19 patients, that could be the leading cause of disease severity and death. Given the high prevalence of Influenza co-infection in our study, increased coverage of flu vaccination is encouraged to mitigate the transmission of influenza virus during the on-going COVID-19 pandemic and reduce the risk of severe outcome and mortality.


Subject(s)
COVID-19/mortality , Coinfection/mortality , Influenza, Human/mortality , Adult , Aged , Bacterial Infections/epidemiology , Bacterial Infections/mortality , Bacterial Infections/pathology , COVID-19/epidemiology , COVID-19/pathology , Coinfection/epidemiology , Coinfection/pathology , Female , Hospitalization , Humans , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/epidemiology , Influenza, Human/pathology , Intensive Care Units , Male , Middle Aged , Nasopharynx/microbiology , Nasopharynx/virology , Prevalence , SARS-CoV-2/isolation & purification , Saudi Arabia/epidemiology
13.
Int J Environ Res Public Health ; 18(12)2021 Jun 10.
Article in English | MEDLINE | ID: covidwho-1264464

ABSTRACT

The human population is currently facing the third and possibly the worst pandemic caused by human coronaviruses (CoVs). The virus was first reported in Wuhan, China, on 31 December 2019 and spread within a short time to almost all countries of the world. Genome analysis of the early virus isolates has revealed high similarity with SARS-CoV and hence the new virus was officially named SARS-CoV-2. Since CoVs have the largest genome among all RNA viruses, they can adapt to many point mutation and recombination events; particularly in the spike gene, which enable these viruses to rapidly change and evolve in nature. CoVs are known to cross the species boundaries by using different cellular receptors. Both animal reservoir and intermediate host for SARS-CoV-2 are still unresolved and necessitate further investigation. In the current review, different aspects of SARS-CoV-2 biology and pathogenicity are discussed, including virus genetics and evolution, spike protein and its role in evolution and adaptation to novel hosts, and virus transmission and persistence in nature. In addition, the immune response developed during SARS-CoV-2 infection is demonstrated with special reference to the interplay between immune cells and their role in disease progression. We believe that the SARS-CoV-2 outbreak will not be the last and spillover of CoVs from bats will continue. Therefore, establishing intervention approaches to reduce the likelihood of future CoVs spillover from natural reservoirs is a priority.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , China/epidemiology , Evolution, Molecular , Humans , Pandemics
14.
J Infect Public Health ; 14(6): 726-733, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1237765

ABSTRACT

BACKGROUND: The uncertainty about COVID-19 outcomes in angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) users continues with contradictory findings. This study aimed to determine the effect of ACEI/ARB use in patients with severe COVID-19. METHODS: This retrospective cohort study was done in two Saudi public specialty hospitals designated as COVID-19 referral facilities. We included 354 patients with a confirmed diagnosis of COVID-19 between April and June 2020, of which 146 were ACEI/ARB users and 208 were non-ACEI/ARB users. Controlling for confounders, we conducted multivariate logistic regression and sensitivity analyses using propensity score matching (PSM) and Inverse propensity score weighting (IPSW) for high-risk patient subsets. RESULTS: Compared to non-ACEI/ARB users, ACEI/ARB users had an eight-fold higher risk of developing critical or severe COVID-19 (OR = 8.25, 95%CI = 3.32-20.53); a nearly 7-fold higher risk of intensive care unit (ICU) admission (OR = 6.76, 95%CI = 2.88-15.89) and a nearly 5-fold higher risk of requiring noninvasive ventilation (OR = 4.77,95%CI = 2.15-10.55). Patients with diabetes, hypertension, and/or renal disease had a five-fold higher risk of severe COVID-19 disease (OR = 5.40,95%CI = 2.0-14.54]. These results were confirmed in the PSM and IPSW analyses. CONCLUSION: In general, but especially among patients with hypertension, diabetes, and/or renal disease, ACEI/ARB use is associated with a significantly higher risk of severe or critical COVID-19 disease, and ICU care.


Subject(s)
Angiotensin Receptor Antagonists , COVID-19 , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Hospitals , Humans , Retrospective Studies , SARS-CoV-2
15.
Curr Med Res Opin ; 37(7): 1085-1097, 2021 07.
Article in English | MEDLINE | ID: covidwho-1199382

ABSTRACT

INTRODUCTION: Favipiravir is a repurposed drug to treat coronavirus 2019 (COVID-19). Due to a lack of available real-world data, we assessed its effectiveness and safety in moderately to critically ill COVID-19 patients. METHODS: This retrospective study was conducted in two public/specialty hospitals in Saudi Arabia. We included patients ≥18 years) admitted April-August 2020 with confirmed SARS-CoV-2 diagnosed by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab. Patients received either favipiravir (1800 mg or 1600 mg twice daily loading dose, followed by 800 mg or 600 mg twice daily) or supportive-care treatment. Patients were excluded if they were outside the study period, classified as having a mild form of the disease per WHO criteria, or had an incomplete patient file. Kaplan-Meier (KM) models were used to estimate median time to discharge. Discharge ratios, progression to mechanical ventilation, and mortality outcomes were estimated across the severity spectrum using Cox proportional-hazards models. As a sensitivity analysis, we performed propensity score-matching (PSM) analysis. RESULTS: Overall, median time to discharge was 10 days (95%CI = 9-10) in the favipiravir arm versus 15 days (95%CI = 14-16) in the supportive-care arm. The accelerated discharge benefit was seen across the COVID-19 spectrum of severity. The adjusted discharge ratio was 1.96 (95%CI = 1.56-2.46). Progression to mechanical ventilation was slower with favipiravir (HRadj = 0.10, 95%CI = 0.04-0.29). There was no significant effect on mortality (HRadj = 1.56, 95%CI = 0.73-3.36). There was a statistically non-significant trend toward worse outcomes in the critical category (HRadj = 2.80, 95%CI = 0.99-7.89). Age was an independent risk factor for mortality in mechanically ventilated patients. PSM analyses confirmed these findings. CONCLUSION: Favipiravir was associated with clinical benefits, including accelerated discharge rate and less progression to mechanical ventilation; however, no overall mortality benefits were seen across the severity spectrum.


Subject(s)
Amides , Antiviral Agents , COVID-19 , Pyrazines , Amides/adverse effects , Amides/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , COVID-19/epidemiology , COVID-19/therapy , Critical Illness/epidemiology , Critical Illness/therapy , Humans , Propensity Score , Pyrazines/adverse effects , Pyrazines/therapeutic use , Respiration, Artificial/statistics & numerical data , Retrospective Studies , SARS-CoV-2 , Saudi Arabia , Sensitivity and Specificity
16.
Viruses ; 13(1)2021 Jan 19.
Article in English | MEDLINE | ID: covidwho-1059930

ABSTRACT

In December 2019, the emergence of SARS-CoV-2 virus in China led to a pandemic. Since both Influenza Like Illness (ILI) and COVID-19 case definitions overlap, we re-investigated the ILI cases using PCR for the presence of SARS-CoV-2 in 739 nasopharyngeal swabs collected from November 2019 to March 2020. SARS-CoV-2 RNA was found in 37 samples (5%) collected mostly during February 2020. It was followed by confirmation of evolutionary and spatial relationships using next generation sequencing (NGS). We observed that the overall incidence of ILI cases during 2019-2020 influenza season was considerably higher than previous years and was gradually replaced with SARS-CoV-2, which indicated a silent transmission among ambulatory patients. Sequencing of representative isolates confirmed independent introductions and silent transmission earlier than previously thought. Evolutionary and spatial analyses revealed clustering in the GH clade, characterized by three amino acid substitutions in spike gene (D614G), RdRp (P323L) and NS3 (Q57H). P323L causes conformational change near nsp8 binding site that might affect virus replication and transcription. In conclusion, assessment of the community transmission among patients with mild COVID-19 illness, particularly those without epidemiological link for acquiring the virus, is of utmost importance to guide policy makers to optimize public health interventions. The detection of SARS-CoV-2 in ILI cases shows the importance of ILI surveillance systems and warrants its further strengthening to mitigate the ongoing transmission of SARS-CoV-2. The effect of NS3 substitutions on oligomerization or membrane channel function (intra- and extracellular) needs functional validation.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , RNA-Dependent RNA Polymerase/metabolism , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/metabolism , Viroporin Proteins/metabolism , Adult , COVID-19/pathology , Disease Transmission, Infectious , Epidemiological Monitoring , Female , Humans , Male , Protein Structure, Secondary , RNA, Viral , RNA-Dependent RNA Polymerase/genetics , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/genetics , Viroporin Proteins/genetics
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