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1.
Forensic Imaging ; : 200508, 2022.
Article in English | ScienceDirect | ID: covidwho-1882003

ABSTRACT

The present study report introduces the roles of radiological technologists (RTs) at Tsukuba Medical Examiner's Office in Japan where a computed tomography system dedicated for examining corpses has been equipped. Several projects and enacted laws regarding postmortem imaging (PMI) have accelerated its use in many Japanese hospitals for detecting causes of death. The lack of sufficient forensic radiologists has led increasing need of RTs to assist forensic pathologists in a timely manner. Optimizing parameters and image processing of postmortem computed tomography (PMCT) and assistance in interpretation of PMCT using checklists by RTs help forensic pathologist to diagnose death causes and select needs for the following autopsy.

2.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-336289

ABSTRACT

The changes that can be observed in the modern world have a huge impact on the English language as they cause an abundance of new words to emerge, mainly in vocabulary and word formation. A large number of neologisms and occasionalisms have appeared in the English language to denote new concepts related to the global spread of coronavirus infection COVID-19 (e.g. quarantine, isolation, remote work, distance learning). This research aims to demonstrate examples of such coroneologisms, to form a classification of the formation methods and to identify the most productive of them. The material for the research was the issues of The Economist (for the period from January to December 2021). During the research the method of complex analysis (selection, classification and description of the material) and the method of component analysis which involves selection and analysis of word components were applied.

3.
Ann Allergy Asthma Immunol ; 2022 May 21.
Article in English | MEDLINE | ID: covidwho-1850617

ABSTRACT

BACKGROUND: mRNA-COVID-19 vaccines have been associated with allergic reactions. A history of anaphylaxis has been suggested as a risk factor for such reactions. Polyethylene glycol (PEG) has been proposed as a possible culprit allergen. OBJECTIVE: To investigate possible PEG or polysorbate allergy among patients reporting prior reactions to COVID-19 vaccines or PEG, and to report their subsequent tolerance of COVID-19 vaccines. METHODS: From January 1 st to October 31 st, 2021, adult patients referred to the MUHC allergy clinics who were considered at risk of anaphylaxis were prospectively recruited. The entry criteria were any documented history of reaction to a COVID-19 vaccine or reported allergy to PEG or polysorbate. Evaluated patients underwent skin-prick-testing (SPT) with PEG and polysorbate. Following SPT, placebo-controlled vaccine challenges were carried out. RESULTS: Of the 44 patients recruited, 40 (90.1%) had reacted to the first vaccine dose, 18 (45%) of them had anaphylactic reaction. All patients underwent SPT and 5 (11.3%) had a positive test. Thirty-nine patients (88.6%) underwent COVID-19 vaccine challenge at the allergy clinic. The majority tolerated the vaccine, 18 (40.1%) received a single full-dose, 20 (45.4%) 2-split-doses and 6 (13.6%) using a graded dosing protocol. Two out of the 40 patients who reacted to 1 st dose, had immediate non-severe allergic reactions to the second dose. CONCLUSION: In this cohort of patients with a history of anaphylaxis and increased risk of allergic reactions to the COVID-19 vaccines, following allergist evaluation, including negative PEG skin testing, the vaccine was safely administered without any serious adverse events.

4.
J Gynecol Obstet Hum Reprod ; 51(5): 102366, 2022 May.
Article in English | MEDLINE | ID: covidwho-1851614

ABSTRACT

OBJECTIVE: To evaluate maternal and neonatal outcomes of pregnant women who were infected by COVID-19 during pregnancy. STUDY DESIGN: A Case control retrospective study was conducted in an Obstetrical Department of a west Parisian area during the first year of COVID-19 pandemic. Maternal and neonatal outcomes were compared between a group of women infected by the SARS-CoV-2 virus during pregnancy (March 2020- February 2021) and a control group of women delivering before pandemic. They were matched according to age and parity. Subgroups of SARS-CoV-2 infection occurring before vs after 37 weeks of gestations and symptomatic vs asymptomatic patients were analyzed. The rate of preterm birth, preeclampsia, placental abruption and stillbirth were compared between the year of pandemic and the year before for all deliveries. RESULTS: Maternal and neonatal outcomes were similar. Among the 86 pregnant women with SARS-CoV-2 infection, five were admitted to Hospital (5.8%). One was transferred in intensive care unit for respiratory distress (1.2%). All patients had favorable outcomes. Patients with symptoms had more associated comorbidities (34.5%, n = 20/58, with symptoms, vs 9,1%, n = 2/22, without symptoms, p = 0.023). No differences in preeclampsia, placenta abruption and stillbirth, but less preterm births (4.9%, n = 160/3383 vs 6.2%, n = 209/3235, p = 0.04) were observed between the year of pandemic and the year before. CONCLUSION: There were few complications associated with COVID-19 infection among pregnant patients and their neonates. A low rate of associated comorbidities, a good access to healthcare services in this area and the small sample size of patients could explain these results.


Subject(s)
COVID-19 , Pre-Eclampsia , Pregnancy Complications, Infectious , Premature Birth , COVID-19/epidemiology , Case-Control Studies , Female , Humans , Infant, Newborn , Pandemics , Placenta , Pre-Eclampsia/epidemiology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Premature Birth/epidemiology , Retrospective Studies , SARS-CoV-2 , Stillbirth/epidemiology
5.
Virus Res ; 315: 198765, 2022 Jul 02.
Article in English | MEDLINE | ID: covidwho-1768587

ABSTRACT

BACKGROUND: Emergence of new variant of SARS-CoV-2, namely omicron, has posed a global concern because of its high rate of transmissibility and mutations in its genome. Researchers worldwide are trying to understand the evolution and emergence of such variants to understand the mutational cascade events. METHODS: We have considered all omicron genomes (n = 302 genomes) available till 2nd December 2021 in the public repository of GISAID along with representatives of variants of concern (VOC), i.e., alpha, beta, gamma, delta, and omicron; variant of interest (VOI) mu and lambda; and variant under monitoring (VUM). Whole genome-based phylogeny and mutational analysis were performed to understand the evolution of SARS CoV-2 leading to emergence of omicron variant. RESULTS: Whole genome-based phylogeny depicted two phylogroups (PG-I and PG-II) forming variant specific clades except for gamma and VUM GH. Mutational analysis detected 18,261 mutations in the omicron variant, majority of which were non-synonymous mutations in spike (A67, T547K, D614G, H655Y, N679K, P681H, D796Y, N856K, Q954H), followed by RNA dependent RNA polymerase (rdrp) (A1892T, I189V, P314L, K38R, T492I, V57V), ORF6 (M19M) and nucleocapsid protein (RG203KR). CONCLUSION: Delta and omicron have evolutionary diverged into distinct phylogroups and do not share a common ancestry. While, omicron shares common ancestry with VOI lambda and its evolution is mainly derived by the non-synonymous mutations.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
6.
Symmetry ; 14(3):579, 2022.
Article in English | ProQuest Central | ID: covidwho-1765925

ABSTRACT

In this paper, the authors describe a set of dynamic chromatography experiments on chiral HPLC columns, and in the range from room temperature to −50 °C for four 1,4-benzodiazepines, extracting the data for the best analytical conditions for their enantiomeric separation. [...]I want to express my great appreciation for the efficient assistance provided to me by Amelia Sun and the Editorial Office of Symmetry. Abbreviations PXRD: powder X-ray diffraction;ESI: electrospray ionization;HPLC: high-performance liquid chromatography;DFT: density functional theory;VCD: vibrational circular dichroism;ECD: electronic circular dichroism;CD: circular dichroism.

7.
Transplantation Proceedings ; 2022.
Article in English | ScienceDirect | ID: covidwho-1747531

ABSTRACT

Introduction : COVID-19 mRNA vaccines have demonstrated excellent short-term safety in phase 3 trials. However, no kidney transplant recipients (KTR) were included. The aim of the study was to assess the safety and tolerability of COVID-19 mRNA vaccines in KTR. Materials and methods : A longitudinal controlled study was conducted in 300 KTR and 143 control patients (CRL) without chronic kidney disease who had received two-dose vaccinations with the mRNA vaccine. Solicited local and systemic reactogenicity, unsolicited adverse events (AE) were assessed with a standardized questionnaire. The toxicity grading scales were derived from the FDA guidelines. Results : KTR (62.7% men) with a median (IQR) age of 53 (41-63) and transplant vintage of 7.25 (3-13) years did not differ with respect to age and sex distribution from CRL. 100% CRL and 83.3% KTR were vaccinated with BNT162b2 (BionTech/Pfizer);16.7% KTR received mRNA-1273 (Moderna) vaccine. Any local reactions were present in 84.7% (1st) and 65.3% (2nd) KTR vs. 67.1% and 60.1% CRL within seven days after the vaccination. Any systemic reactions were reported by 26.7% (1st) and 20.9% (2nd) KTR vs. 24.7 and 35.7% CRL. The most common systemic reactions in KTR were: fatigue, headache and myalgia. No serious AE were observed. Many systemic reactions were observed less frequently in KTR than CRL. Younger KTR (<54 years) reported any local and any systemic reactions significantly more frequently than older patients. Conclusions : mRNA COVID-19 vaccines are safe and well-tolerated by KTR. The results may resolve patients' doubts and reduce their vaccine hesitancy.

8.
BBA Adv ; 2: 100044, 2022.
Article in English | MEDLINE | ID: covidwho-1676410

ABSTRACT

Once inhaled, SARS-CoV-2 particles enter respiratory ciliated cells by interacting with angiotensin converting enzyme 2 (ACE2). Understanding the nature of ACE2 within airway tissue has become a recent focus particularly in light of the COVID-19 pandemic. Airway mucociliary tissue was generated in-vitro using primary human nasal epithelial cells and the air-liquid interface (ALI) model of differentiation. Using ALI tissue, three distinct transcript variants of ACE2 were identified. One transcript encodes the documented full-length ACE2 protein. The other two transcripts are unique truncated isoforms, that until recently had only been predicted to exist via sequence analysis software. Quantitative PCR revealed that all three transcript variants are expressed throughout differentiation of airway mucociliary epithelia. Immunofluorescence analysis of individual ACE2 protein isoforms exogenously expressed in cell-lines revealed similar abilities to localize in the plasma membrane and interact with the SARS CoV 2 spike receptor binding domain. Immunohistochemistry on differentiated ALI tissue using antibodies to either the N-term or C-term of ACE2 revealed both overlapping and distinct signals in cells, most notably only the ACE2 C-term antibody displayed plasma-membrane localization. We also demonstrate that ACE2 protein shedding is different in ALI Tissue compared to ACE2-transfected cell lines, and that ACE2 is released from both the apical and basal surfaces of ALI tissue. Together, our data highlights various facets of ACE2 transcripts and protein in airway mucociliary tissue that may represent variables which impact an individual's susceptibility to SARS-CoV-2 infection, or the severity of Covid-19.

9.
Neuroimmunology Reports ; : 100053, 2021.
Article in English | ScienceDirect | ID: covidwho-1586941

ABSTRACT

Background Literature describing triggers of GFAP astrocytopathy (GFAP-A) is limited. We report a case of GFAP-A in a patient with recent messenger ribonucleic acid (mRNA) severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) vaccination and discuss the possible pathogenesis. Case description A 45-year-old gentleman presented with features of meningoencephalitis 31 days after the first dose and 4 days after the second dose of mRNA SARS-CoV-2 vaccination. He sequentially developed brainstem/cerebellar, autonomic and cord dysfunction. Cerebrospinal fluid was positive for GFAP autoantibody. Clinical improvement occurred after intravenous methylprednisolone and immunoglobulins. Conclusion Although we are uncertain of a causal link of GFAP-A to mRNA vaccine, indirect activation of an underlying dysregulated immune milieu is plausible.

10.
S Afr J Bot ; 2021 Dec 03.
Article in English | MEDLINE | ID: covidwho-1550057

ABSTRACT

Coronaviruses (CoVs) are a large group of enveloped positive sense single-stranded RNA viruses that can cause disease to humans. These are zoonotic having potential to cause large-scale outbreaks of infections widely causing morbidity and mortality. Papain-Like Proteases (PLpro) is a cysteine protease, essential for viral replication and proliferation, as a highly conserved enzyme it cleaves peptide linkage between Nsp1, Nsp2, Nsp3, and Nsp4. As a valid therapeutic targets it stops viral reproduction and boosts host immune response thereby halting further spread of infection. In the purpose of identifying inhibitors targeting Papain-Like Proteases (PLpro) we initiated a high throughput virtual screening (HTVS) protocol using a SuperNatural Database. The XP docking results revealed that two compounds SN00334175 and SN00162745 exhibited docking score of -10.58 kcal/mol and -9.93 kcal/mol respectively. The Further PRIME MMGB-SA studies revealed Van der Waal energy and hydrophobic energy terms as major contributors for total binding free energy. The 100 ns molecular dynamics simulation of SN00334175/7JN2 and SN00162745/7JN2 revealed that these complexes were stabilized with ligand binding forming interactions with Gly266, Asn267, Tyr268, Tyr273, Thr301 and Asp302, Lys157, Leu162, Asp164, Arg166, Glu167, Pro248, Tyr264.

11.
J Clin Epidemiol ; : 107-120, 2021 Jul 02.
Article in English | MEDLINE | ID: covidwho-1466591

ABSTRACT

OBJECTIVES: To assess the reporting quality of abstracts for published randomized controlled trials (RCTs) of interventions for coronavirus disease 2019 (COVID-19), including the use of spin strategies and the level of spin for RCTs with statistically non-significant primary outcomes, and to explore potential predictors for reporting quality and the severity of spin. STUDY DESIGN AND SETTING: PubMed was searched to find RCTs that tested interventions for COVID-19, and the reporting quality and spin in the abstracts were assessed. Linear regression analyses were used to identify potential predictors. RESULTS: Forty RCT abstracts were included in our assessment of reporting quality, and a higher word count in the abstract was significantly correlated with higher reporting scores (95% CI 0.044 to 0.658, P=0.026). Multiple spin strategies were identified. Our multivariate analyses showed that geographical origin was associated with severity of spin, with research from non-Asian regions containing fewer spin strategies (95% CI -0.760 to -0.099, P=0.013). CONCLUSIONS: The reporting quality of abstracts of RCTs of interventions for COVID-19 is far from satisfactory. A relatively high proportion of the abstracts contained spin, and the findings reported in the results and conclusion sections of these abstracts need to be interpreted with caution.

12.
Ann Epidemiol ; 63: 46-51, 2021 11.
Article in English | MEDLINE | ID: covidwho-1351545

ABSTRACT

PURPOSE: To examine neighborhood-level disparities in SARS-CoV-2 molecular test percent positivity in New York City (NYC) by demographics and socioeconomic status over time to better understand COVID-19 inequities. METHODS: Across 177 neighborhoods, we calculated the Spearman correlation of neighborhood characteristics with SARS-CoV-2 molecular test percent positivity during March 1-July 25, 2020 by five periods defined by trend in case counts: increasing, declining, and three plateau periods to account for differential testing capacity and reopening status. RESULTS: Percent positivity was positively correlated with neighborhood racial and ethnic characteristics and socioeconomic status, including the proportion of the population who were Latino and Black non-Latino, uninsured, Medicaid enrollees, transportation workers, or had low educational attainment. Correlations were generally consistent over time despite increasing testing rates. Neighborhoods with high proportions of these correlates had median percent positivity values of 62.6%, 28.7%, 6.4%, 2.8%, and 2.2% in the five periods, respectively, compared with 40.6%, 11.7%, 1.7%, 0.9%, and 1.0% in neighborhoods with low proportions of these correlates. CONCLUSIONS: Disparities in SARS-CoV-2 molecular test percent positivity persisted in disadvantaged neighborhoods during multiple phases of the first few months of the COVID-19 epidemic in NYC. Mitigation of the COVID-19 burden is still urgently needed in disproportionately affected communities.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , New York City/epidemiology , Residence Characteristics , Socioeconomic Factors
13.
J Pediatr Surg ; 2021 Jul 16.
Article in English | MEDLINE | ID: covidwho-1313276

ABSTRACT

BACKGROUND: Testicular torsion is a pediatric surgical emergency, and prompt diagnosis and treatment is imperative. During the COVID-19 pandemic, pediatric patients with symptoms of testicular torsion may be reluctant to seek medical care which increases the likelihood of delayed presentation and the need for an orchiectomy. This observational study sought to determine whether there was a higher number of testicular torsion cases during COVID-19. METHODS: As the first patient with COVID-19 was admitted to our facility on March 6, 2020, we identified male children ages 1-18 years with testicular torsion between March 1-December 31, 2020 (during COVID-19) compared to the same time period between 2015 and 2019 (prior to COVID-19). All patients were evaluated at our Institution's Emergency Department by a pediatric urologist. RESULTS: There were 38 cases of testicular torsion between March 1-December 31, 2020 compared to 15.8 cases on average during the same 10-month period between 2015 and 2019 (a total of 79 cases). There was a statistically significant increase in testicular torsion cases during the COVID-19 pandemic compared to equivalent time periods in 2015-2019 (38 vs. 15.8, p = 0.05). Patients with testicular torsion during the COVID-19 pandemic were younger, had a longer duration of symptoms, and had a higher number of orchiectomies (although not statistically significant). CONCLUSION: During the COVID-19 pandemic, an escalation in testicular torsion cases was observed. Timely assessment, diagnosis, and surgery are crucial to prevent testicular loss and potential infertility in the future. Further evaluation is needed to elucidate the surge in testicular torsion and possible mechanisms.

14.
J Surg Educ ; 79(1): 229-236, 2022.
Article in English | MEDLINE | ID: covidwho-1294011

ABSTRACT

OBJECTIVE: Social distancing restrictions due to COVID-19 challenged our ability to educate incoming surgery interns who depend on early simulation training for basic skill acquisition. This study aimed to create a proficiency-based laparoscopic skills curriculum using remote learning. DESIGN: Content experts designed 5 surgical tasks to address hand-eye coordination, depth perception, and precision cutting. A scoring formula was used to measure performance: cutoff time - completion time - (K × errors) = score; the constant K was determined for each task. As a benchmark for proficiency, a fellowship-trained laparoscopic surgeon performed 3 consecutive repetitions of each task; proficiency was defined as the surgeon's mean score minus 2 standard deviations. To train remotely, PGY1 surgery residents (n = 29) were each issued a donated portable laparoscopic training box, task explanations, and score sheets. Remote training included submitting a pre-test video, self-training to proficiency, and submitting a post-test video. Construct validity (expert vs. trainee pre-tests) and skill acquisition (trainee pre-tests vs. post-tests) were compared using a Wilcoxon test (median [IQR] reported). SETTING: The University of Texas Southwestern Medical Center in Dallas, Texas PARTICIPANTS: Surgery interns RESULTS: Expert and trainee pre-test performance was significantly different for all tasks, supporting construct validity. One trainee was proficient at pre-test. After 1 month of self-training, 7 additional residents achieved proficiency on all 5 tasks after 2-18 repetitions; trainee post-test scores were significantly improved versus pre-test on all tasks (p = 0.01). CONCLUSIONS: This proficiency-based curriculum demonstrated construct validity, was feasible as a remote teaching option, and resulted in significant skill acquisition. The remote format, including video-based performance assessment, facilitates effective at-home learning and may allow additional innovations such as video-based coaching for more advanced curricula.


Subject(s)
COVID-19 , Internship and Residency , Laparoscopy , Clinical Competence , Curriculum , Humans , SARS-CoV-2
15.
Ann Epidemiol ; 59: 50-55, 2021 07.
Article in English | MEDLINE | ID: covidwho-1198609

ABSTRACT

PURPOSE: Contact tracing is intended to reduce the spread of coronavirus disease 2019 (COVID-19), but it is difficult to conduct among people who live in congregate settings, including people experiencing homelessness (PEH). This analysis compares person-based contact tracing among two populations in Salt Lake County, Utah, from March-May 2020. METHODS: All laboratory-confirmed positive cases among PEH (n = 169) and documented in Utah's surveillance system were included in this analysis. The general population comparison group (n = 163) were systematically selected from all laboratory-confirmed cases identified during the same period. RESULTS: Ninety-three PEH cases (55%) were interviewed compared to 163 (100%) cases among the general population (P < .0001). PEH were more likely to be lost to follow-up at end of isolation (14.2%) versus the general population (0%; P-value < .0001) and provided fewer contacts per case (0.3) than the general population (4.7) (P-value < .0001). Contacts of PEH were more often unreachable (13.0% vs. 7.1%; P-value < .0001). CONCLUSIONS: These findings suggest that contact tracing among PEH should include a location-based approach, along with a person-based approach when resources allow, due to challenges in identifying, locating, and reaching cases among PEH and their contacts through person-based contact tracing efforts alone.


Subject(s)
COVID-19 , Homeless Persons , Contact Tracing , Humans , SARS-CoV-2 , Utah/epidemiology
16.
Eur J Intern Med ; 86: 41-47, 2021 04.
Article in English | MEDLINE | ID: covidwho-1084315

ABSTRACT

BACKGROUND: The influence of aging and multimorbidity on Covid-19 clinical presentation is still unclear. OBJECTIVES: We investigated whether the association between symptoms (or cluster of symptoms) and positive SARS-CoV-2 nasopharyngeal swab (NPS) was different according to patients' age and presence of multimorbidity. METHODS: The study included 6680 participants in the EPICOVID19 web-based survey, who reported information about symptoms from February to June 2020 and who underwent at least one NPS. Symptom clusters were identified through hierarchical cluster analysis. The associations between symptoms (and clusters of symptoms) and positive NPS were investigated through multivariable binary logistic regression in the sample stratified by age (<65 vs ≥65 years) and number of chronic diseases (0 vs 1 vs ≥2). RESULTS: The direct association between taste/smell disorders and positive NPS was weaker in older and multimorbid patients than in their younger and healthier counterparts. Having reported no symptoms reduced the chance of positive NPS by 86% in younger (95%CI: 0.11-0.18), and by 46% in older participants (95%CI: 0.37-0.79). Of the four symptom clusters identified (asymptomatic, generic, flu-like, and combined generic and flu-like symptoms), those associated with a higher probability of SARS-CoV-2 infection were the flu-like for older people, and the combined generic and flu-like for the younger ones. CONCLUSIONS: Older age and pre-existing chronic diseases may influence the clinical presentation of Covid-19. Symptoms at disease onset tend to aggregate differently by age. New diagnostic algorithms considering age and chronic conditions may ease Covid-19 diagnosis and optimize health resources allocation. TRIAL REGISTRATION: NCT04471701 (ClinicalTrials.gov).


Subject(s)
COVID-19 , Aged , Aged, 80 and over , COVID-19 Testing , Humans , Internet , SARS-CoV-2 , Surveys and Questionnaires
17.
Gene Rep ; 21: 100886, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1023577

ABSTRACT

Since December 2019, a severe pandemic of pneumonia, COVID-19 associated with a novel coronavirus (SARS-CoV-2), have emerged in Wuhan, China and spreading throughout the world. As RNA viruses have a high mutation rate therefore we wanted to identify whether this virus is also prone to mutations. For this reason we selected four major structural (Spike protein (S), Envelope protein (E), Membrane glycoprotein (M), Nucleocapsid phosphoprotein (N)) and ORF8 protein of 100 different SARS-CoV-2 isolates of fifteen countries from NCBI database and compared these to the reference sequence, Wuhan NC_045512.2, which was the first isolate of SARS-CoV-2 that was sequenced. By multiple sequence alignment of amino acids, we observed substitutions and deletion in S protein at 13 different sites in the isolates of five countries (China, USA, Finland, India and Australia) as compared to the reference sequence. Similarly, alignment of N protein revealed substitutions at three different sites in isolates of China, Spain and Japan. M protein exhibits substitution only in one isolates from USA, however, no mutation was observed in E protein of any isolate. Interestingly, in ORF8 substitution of Leucine, a nonpolar to Serine a polar amino acid at same position (aa84 L to S) in 23 isolates of five countries i.e. China, USA, Spain, Taiwan and India were observed, which may affect the conformation of peptides. Thus, we observed several mutations in the isolates thereafter the first sequencing of SARS-CoV-2 isolate, NC_045512.2, which suggested that this virus might be a threat to the whole world and therefore further studies are needed to characterize how these mutations in different proteins affect the functionality and pathogenesis of SARS-CoV-2.

18.
Indian J Pharmacol ; 52(4): 313-323, 2020.
Article in English | MEDLINE | ID: covidwho-881413

ABSTRACT

BACKGROUND: Being protease inhibitors and owing to their efficacy in SARS-CoV, lopinavir + ritonavir (L/R) combination is being used in the management of COVID-19. In this systematic review and meta-analysis, we have evaluated the comparative safety and efficacy of L/R combination. MATERIALS AND METHODS: Comparative, observational studies and controlled clinical trials comparing L/R combination to standard of care (SOC)/control or any other antiviral agent/combinations were included. A total of 10 databases were searched to identify 13 studies that fulfilled the predefined inclusion/exclusion criteria. RESULTS: No discernible beneficial effect was seen in the L/R group in comparison to SOC/control in terms of "progression to more severe state" (4 studies, odds ratio [OR]: 1.446 [0.722-2.895]), "mortality" (3 studies, OR: 1.208 [0.563-2.592]), and "virological cure on days 7-10" (3 studies, OR: 0.777 [0.371-1.630]), while the L/R combination arm performed better than the SOC/control arm in terms of "duration of hospital stay" (3 studies, mean difference (MD): -1.466 [-2.403 to - 0.529]) and "time to virological cure" (3 studies, MD: -3.272 [-6.090 to - 0.454]). No difference in efficacy was found between L/R versus hydroxychloroquine (HCQ) and L/R versus arbidol. However, in a single randomized controlled trail (open label), chloroquine (CQ) performed better than L/R. The combination L/R with arbidol may be beneficial (in terms of virological clearance and radiological improvement); however, we need more dedicated studies. Single studies report efficacy of L/R + interferon (IFN, either alpha or 1-beta) combination. We need more studies to delineate the proper effect size. Regarding adverse effects, except occurrence of diarrhea (higher in the L/R group), safety was comparable to SOC. CONCLUSION: In our study, no difference was seen between the L/R combination and the SOC arm in terms of "progression to more severe state," "mortality," and virological cure on days 7-10;" however, some benefits in terms of "duration of hospital stay" and "time to virological cure" were seen. No significant difference in efficacy was seen when L/R was compared to arbidol and HCQ monotherapy. Except for the occurrence of diarrhea, which was higher in the L/R group, safety profile of L/R is comparable to SOC. Compared to L/R combination, CQ, L/R + arbidol, L/R + IFN-α, and L/R + IFN-1ß showed better efficacy, but the external validity of these findings is limited by limited number of studies (1 study each).


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Lopinavir/therapeutic use , Pneumonia, Viral/drug therapy , Ritonavir/therapeutic use , COVID-19 , Drug Combinations , Humans , Negative Results , Pandemics , Treatment Outcome
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