Project description:The devastating pandemic due to SARS-CoV-2 and the emergence of antigenic variants that jeopardize the efficacy of current vaccines create an urgent need for a comprehensive understanding of the pathophysiology of COVID-19, including the contribution of inflammation to disease. It also warrants for the search of immunomodulatory drugs that could improve disease outcome. Here, we show that standard doses of ivermectin (IVM), an anti-parasitic drug with potential immunomodulatory activities through the cholinergic anti-inflammatory pathway, prevents clinical deterioration, reduces olfactory deficit and limits the inflammation of the upper and lower respiratory tracts in SARS-CoV-2-infected hamsters. Whereas it has no effect on viral load in the airways of infected animals, transcriptomic analyses of infected lungs reveal that IVM dampens type-I interferon responses and modulates several other inflammatory pathways. In particular, IVM dramatically reduces the Il-6/Il-10 ratio in lung tissue and promotes macrophage M2 polarization, which might account for the more favorable clinical presentation of IVM-treated animals. Altogether, this study supports the use of immunomodulatory drugs such as IVM, to improve the clinical condition of SARS-CoV-2-infected patients.
Project description:Severe acute respiratory syndrome virus (SARS-CoV-2) has infected millions of people worldwide. Our goal was to identify risk factors associated with admission and disease severity in patients with SARS-CoV-2. This was an observational, retrospective study based on real-world data for 7,995 patients with SARS-CoV-2 from a clinical data repository. Yale New Haven Health (YNHH) is a five-hospital academic health system serving a diverse patient population with community and teaching facilities in both urban and suburban areas. The study included adult patients who had SARS-CoV-2 testing at YNHH between March 1 and April 30, 2020. Primary outcomes were admission and in-hospital mortality for patients with SARS-CoV-2 infection as determined by RT-PCR testing. We also assessed features associated with the need for respiratory support. Of the 28605 patients tested for SARS-CoV-2, 7995 patients (27.9%) had an infection (median age 52.3 years) and 2154 (26.9%) of these had an associated admission (median age 66.2 years). Of admitted patients, 2152 (99.9%) had a discharge disposition at the end of the study period. Of these, 329 (15.3%) required invasive mechanical ventilation and 305 (14.2%) expired. Increased age and male sex were positively associated with admission and in-hospital mortality (median age 80.7 years), while comorbidities had a much weaker association with the risk of admission or mortality. Black race (OR 1.43, 95%CI 1.14-1.78) and Hispanic ethnicity (OR 1.81, 95%CI 1.50-2.18) were identified as risk factors for admission, but, among discharged patients, age-adjusted in-hospital mortality was not significantly different among racial and ethnic groups. This observational study identified, among people testing positive for SARSCoV-2 infection, older age and male sex as the most strongly associated risks for admission and in-hospital mortality in patients with SARS-CoV-2 infection. While minority racial and ethnic groups had increased burden of disease and risk of admission, age-adjusted in-hospital mortality for discharged patients was not significantly different among racial and ethnic groups. Ongoing studies will be needed to continue to evaluate these risks, particularly in the setting of evolving treatment guidelines.
Project description:ObjectiveSevere acute respiratory syndrome virus (SARS-CoV-2) has infected millions of people worldwide. Our goal was to identify risk factors associated with admission and disease severity in patients with SARS-CoV-2.DesignThis was an observational, retrospective study based on real-world data for 7,995 patients with SARS-CoV-2 from a clinical data repository.SettingYale New Haven Health (YNHH) is a five-hospital academic health system serving a diverse patient population with community and teaching facilities in both urban and suburban areas.PopulationsThe study included adult patients who had SARS-CoV-2 testing at YNHH between March 1 and April 30, 2020.Main outcome and performance measuresPrimary outcomes were admission and in-hospital mortality for patients with SARS-CoV-2 infection as determined by RT-PCR testing. We also assessed features associated with the need for respiratory support.ResultsOf the 28605 patients tested for SARS-CoV-2, 7995 patients (27.9%) had an infection (median age 52.3 years) and 2154 (26.9%) of these had an associated admission (median age 66.2 years). Of admitted patients, 2152 (99.9%) had a discharge disposition at the end of the study period. Of these, 329 (15.3%) required invasive mechanical ventilation and 305 (14.2%) expired. Increased age and male sex were positively associated with admission and in-hospital mortality (median age 80.7 years), while comorbidities had a much weaker association with the risk of admission or mortality. Black race (OR 1.43, 95%CI 1.14-1.78) and Hispanic ethnicity (OR 1.81, 95%CI 1.50-2.18) were identified as risk factors for admission, but, among discharged patients, age-adjusted in-hospital mortality was not significantly different among racial and ethnic groups.ConclusionsThis observational study identified, among people testing positive for SARS-CoV-2 infection, older age and male sex as the most strongly associated risks for admission and in-hospital mortality in patients with SARS-CoV-2 infection. While minority racial and ethnic groups had increased burden of disease and risk of admission, age-adjusted in-hospital mortality for discharged patients was not significantly different among racial and ethnic groups. Ongoing studies will be needed to continue to evaluate these risks, particularly in the setting of evolving treatment guidelines.
Project description:BackgroundThere is limited information describing the characteristics and outcomes of hospitalized older patients with confirmed coronavirus disease 2019 (COVID-19).MethodWe conducted a multicentric retrospective cohort study in 13 acute COVID-19 geriatric wards, from March 13 to April 15, 2020, in Paris area. All consecutive patients aged 70 years and older, with confirmed COVID-19, were enrolled.ResultsOf the 821 patients included in the study, the mean (SD) age was 86 (7) years; 58% were female; 85% had ≥2 comorbidities; 29% lived in an institution; and the median [interquartile range] Activities of Daily Living scale (ADL) score was 4 [2-6]. The most common symptoms at COVID-19 onset were asthenia (63%), fever (55%), dyspnea (45%), dry cough (45%), and delirium (25%). The in-hospital mortality was 31% (95% confidence interval [CI] 27-33). On multivariate analysis, at COVID-19 onset, the probability of in-hospital mortality was increased with male gender (odds ratio [OR] 1.85; 95% CI 1.30-2.63), ADL score <4 (OR 1.84; 95% CI 1.25-2.70), asthenia (OR 1.59; 95% CI 1.08-2.32), quick Sequential Organ Failure Assessment score ≥2 (OR 2.63; 95% CI 1.64-4.22), and specific COVID-19 anomalies on chest computerized tomography (OR 2.60; 95% CI 1.07-6.46).ConclusionsThis study provides new information about older patients with COVID-19 who are hospitalized. A quick bedside evaluation at admission of sex, functional status, systolic arterial pressure, consciousness, respiratory rate, and asthenia can identify older patients at risk of unfavorable outcomes.
Project description:BackgroundThis study aimed to analyze clinical and multimodal imaging characteristics of acute macular neuroretinopathy (AMN) post-recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.MethodsRetrospective observational study. Medical records and multimodal imaging of 12 AMN eyes of eight patients (six female and two male) with recent SARS-CoV-2 infection were retrospectively analyzed.ResultsFour patients (50%) presented with bilateral AMN. Fundus ophthalmoscopy revealed a reddish-brown lesion around the macula, and two eyes had cotton-wool spots at the posterior pole. Three eyes showed mild hypo-autofluorescence. All FFA images (7 eyes) showed no abnormal signs. On OCT scans, all eyes showed outer nuclear layer (ONL) thinning, 8 eyes (66.7%) showed ONL hyperreflectivity, 5 eyes (41.7%) showed outer plexiform layer (OPL) hyperreflectivity, 8 eyes (66.7%) showed interdigitation zone (IZ) disruption, 11 eyes (91.6%) showed ellipsoid zone (EZ) disruption, 2 eyes (16.7%) showed cotton-wool spots and inner plexiform layer (IPL) hyperreflectivity, 1 eye (8.3%) had intraretinal cyst and 1 eye (8.3%) had inner nuclear layer (INL) thinning. Persistent scotoma, ONL hyperreflectivity and IZ/EZ disruption as well as recovery of OPL hyperreflectivity were reported after follow-up in three cases.ConclusionsAMN post-SARS-CoV-2 mostly affected young females and could present unilaterally or bilaterally. Dark lesions on IR reflectance and outer retinal hyperreflectivity on OCT are useful in diagnosing AMN. OPL/ONL hyperreflectivity on OCT could disappear after follow-up, but ONL thinning and IZ/EZ could persist.
Project description:BackgroundA retrospective study was conducted to summarize the clinical information of childhood infections during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic.MethodsChildren with SARS-CoV-2 infection in 11 hospitals from three provinces of South China were included in the study. Clinical information was collected and compared with children and adults infected by SARS-CoV-2 in Wuhan.ResultsIn total, 52 children were enrolled, including 28 boys. The median age was 9 years (interquartile range [IQR], 4-12); 44.2% cases were of clustered occurrences, 40.4% patients had fever, 48.1% had cough, and 46.2% had a high lymphocyte count. No abnormalities were found in the liver and kidney function. Also, 82.7% of patients received antiviral therapy, but such therapy did not shorten the time to virus negativity or hospital stay (P = .082). The time to virus negativity was 12.0 days (IQR, 8.0-16.8) and hospital stay was 14.5 days (IQR, 10.3-17.9). Compared with reports in Wuhan, there were more acute upper respiratory tract infection (AURTI) and fewer pneumonia cases (P = .000). Compared with the non-ICU adult COVID-19 in Wuhan, these children's diseases were relatively mild, with fewer complications.ConclusionsChildren with SARS-CoV-2 infection had a mild fever, lymphocyte elevation was more common than reduction, and antiviral treatment had no obvious effect. The overall clinical manifestations were mild, and the prognosis was good.
Project description:In December 2019, a cluster of pneumonia cases was caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China. Cancer patients are a special group, the immunity of them will be suppressed because of various anti-tumor treatments, and the risk of infection will be greatly increased, so we will report clinical features of 9 cancer patients with SARS-CoV-2 infection. 5 (56%) patients were ordinary type, 3 (33%) were severe type, and 1 (11%) was critical type. A total of 8 patients received combined therapy of traditional Chinese medicines and western medicines. From the clinical outcomes of these 8 patients, western combined therapy of traditional Chinese medicine was indeed an effective treatment method. D-dimmer rise, infection index rise, and chest CT(computed tomography) progression may be clinical warning indicators for severe patients, in our study, more 50% of patients had elevated levels of these indicators, but only 44% (including the dead) of patients had received treatment in the intensive care unit. 5 (56%) ordinary type patients had been discharged, while the 1 (11%) critical type patient died 3 days after admission. Cancer comorbidity seems to have no direct relationship with severe events, and the combination of traditional Chinese medicine and western medicine may be effective in the prevention and treatment of novel coronavirus-infected pneumonia (NICP).
Project description:BackgroundCommunity clustering is one of the main features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, few studies have been conducted on the clinical characteristics and clinical outcome of clustered cases and sporadic cases with COVID-19.MethodsWe recruited 41 community clusters confirmed with SARS-CoV-2 infection compared with 49 sporadic cases in Zhejiang Province from 19 January 2020 to 9 June 2020. Clinical data were collected to evaluate the clinical outcome and characteristics of community clusters.ResultsCompared to sporadic cases, clustered cases had significantly lower Acute Physiology and Chronic Health Evaluation II (APACHE II) score {5.0 [interquartile range (IQR), 2.0-7.5] vs. 7.0 [IQR, 4.0-12.5]; P = 0.005}, less members in intensive care unit (ICU) (6 [14.6%] vs. 18 [36.7%]; P = 0.018), and shorter time of viral shedding in fecal samples (18.5 [IQR, 17.0-28.3] vs. 32.0 [IQR, 24.3-35.5]; P = 0.002). Univariable logistic regression revealed that older age (odds ratios 1.078, 95% confidence intervals 1.007-1.154, per year increase; p = 0.032), high APACHE II score (3.171, 1.147-8.76; P = 0.026), elevated interleukin-2 levels (3.078, 1.145-8.279; P = 0.026) were associated with ICU admission of clustered cases.ConclusionsCompared to sporadic cases, clustered cases exhibited milder disease severity and a better clinical outcome, which may be closely related to the management of early detection, early diagnosis, early treatment and early isolation of COVID-19.
Project description:ObjectivesTo compare the clinical and epidemiological aspects associated with different predominant lineages circulating in Marseille from March 2020 to January 2021.MethodsIn this single-centre retrospective cohort study, characteristics of patients infected with four different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were documented from medical files. The outcome was the occurrence of clinical failure, defined as hospitalization (for outpatients), transfer to the intensive care unit (inpatients) and death (all).ResultsA total of 254 patients were infected with clade 20A (20AS), 85 with Marseille-1 (M1V), 190 with Marseille-4 (M4V) and 211 with N501Y (N501YV) variants. 20AS presented a bell-shaped epidemiological curve and nearly disappeared around May 2020. M1V reached a very weak peak, then disappeared after six weeks. M4V appeared in July presented an atypical wave form for 7 months. N501YV has only recently appeared. Compared with 20AS, patients infected with M1V were less likely to report dyspnoea (adjusted odds ratio (OR) 0.50, p 0.04), rhinitis (aOR 0.57, p 0.04) and to be hospitalized (aOR 0.22, p 0.002). Patients infected with M4V were more likely to report fever than those with 20AS and M1V (aOR 2.49, p < 0.0001 and aOR 2.30, p 0.007, respectively) and to be hospitalized than those with M1V (aOR 4.81, p 0.003). Patients infected with N501YV reported lower rate of rhinitis (aOR 0.50, p 0.001) and anosmia (aOR 0.57, p 0.02), compared with those infected with 20AS. A lower rate of hospitalization was associated with N501YV infection compared with 20AS and M4V (aOR 0.33, p < 0.0001 and aOR 0.27, p < 0.0001, respectively).ConclusionsThe four lineages have presentations that differ from one another, epidemiologically and clinically. This supports SARS-CoV-2 genomic surveillance through next-generation sequencing.