Modeling non-pharmaceutical interventions in the COVID-19 pandemic with survey-based simulations.

Governments around the globe use non-pharmaceutical interventions (NPIs) to curb the spread of coronavirus disease 2019 (COVID-19) cases. Making decisions under uncertainty, they all face the same temporal paradox: estimating the impact of NPIs before they have been implemented. Due to the limited variance of empirical cases, researchers could so far not disentangle effects of individual NPIs or their impact on different demographic groups. In this paper, we utilize large-scale agent-based simulations in combination with Susceptible-Exposed-Infectious-Recovered (SEIR) models to investigate the spread of COVID-19 for some of the most affected federal states in Germany. In contrast to other studies, we sample agents from a representative survey. Including more realistic demographic attributes that influence agents' behavior yields accurate predictions of COVID-19 transmissions and allows us to investigate counterfactual what-if scenarios. Results show that quarantining infected people and exploiting industry-specific home office capacities are the most effective NPIs. Disentangling education-related NPIs reveals that each considered institution (kindergarten, school, university) has rather small effects on its own, yet, that combined openings would result in large increases in COVID-19 cases. Representative survey-characteristics of agents also allow us to estimate NPIs' effects on different age groups. For instance, re-opening schools would cause comparatively few infections among the risk-group of people older than 60 years.

Impact of early corticosteroids on 60-day mortality in critically ill patients with COVID-19: A multicenter cohort study of the OUTCOMEREA network.

OBJECTIVES: In severe COVID-19 pneumonia, the appropriate timing and dosing of corticosteroids (CS) is not known. Patient subgroups for which CS could be more beneficial also need appraisal. The aim of this study was to assess the effect of early CS in COVID-19 pneumonia patients admitted to the ICU on the occurrence of 60-day mortality, ICU-acquired-bloodstream infections(ICU-BSI), and hospital-acquired pneumonia and ventilator-associated pneumonia(HAP-VAP). METHODS: We included patients with COVID-19 pneumonia admitted to 11 ICUs belonging to the French OutcomeReaTM network from January to May 2020. We used survival models with ponderation with inverse probability of treatment weighting (IPTW). RESULTS: The study population comprised 303 patients having a median age of 61.6 (53-70) years of whom 78.8% were male and 58.6% had at least one comorbidity. The median SAPS II was 33 (25-44). Invasive mechanical ventilation was required in 34.8% of the patients. Sixty-six (21.8%) patients were in the Early-C subgroup. Overall, 60-day mortality was 29.4%. The risks of 60-day mortality (IPTWHR = 0.86;95% CI 0.54 to 1.35, p = 0.51), ICU-BSI and HAP-VAP were similar in the two groups. Importantly, early CS treatment was associated with a lower mortality rate in patients aged 60 years or more (IPTWHR, 0.53;95% CI, 0.3-0.93; p = 0.03). In contrast, CS was associated with an increased risk of death in patients younger than 60 years without inflammation on admission (IPTWHR = 5.01;95% CI, 1.05, 23.88; p = 0.04). CONCLUSION: For patients with COVID-19 pneumonia, early CS treatment was not associated with patient survival. Interestingly, inflammation and age can significantly influence the effect of CS.

Role of the early short-course corticosteroids treatment in ARDS caused by COVID-19: A single-center, retrospective analysis.

PURPOSE: Severe coronavirus disease 2019 (COVID-19) is strongly related to interstitial pneumonia with frequent development of acute respiratory distress syndrome (ARDS). The role of corticosteroids (CS) treatment in these patients is still controversial. Some studies evidenced a possible role of an early short-term course of CS treatment in the treatment of severe pneumonia. PATIENTS AND METHODS: This is a single-center, retrospective study considering the patients with confirmed COVID-19 pneumonia admitted to our hospital between 9th March and 15th June 2020. Two groups were considered: early high-dose of methyl-prednisolone (eHDM; n â€‹= â€‹31) and the control group (n â€‹= â€‹52). Patients in the eHDM group received the dose of 5-8 â€‹mg/kg/day of methyl-prednisolone for 2 consecutive days. Primary outcome was the mortality evaluation; secondary outcomes were clinical improvement, side-effects and laboratory/radiographic changes. RESULTS: Significant differences between the two groups were: length of hospitalization (21.5 vs 28.4 days, p â€‹= â€‹0.026), length of non-invasive ventilation (NIV) or mechanical ventilation (11.5 vs 14.5 days, p â€‹= â€‹0.031), death (5 vs 12, p â€‹= â€‹0.006) and clinical improvement (16 vs 11, p=0.018). The following factors were related to in-hospital mortality in the multivariate analysis: comorbidities (OR â€‹= â€‹2.919; 95%CI â€‹= â€‹1.515-16.705; p<0.001), days from the onset of symptoms and the hospital admission (OR â€‹= â€‹1.404; 95%CI â€‹= â€‹1.069-12.492; p â€‹= â€‹0.011), PaO2/FiO2 (P/F) ratio (OR â€‹= â€‹3.111; 95%CI â€‹= â€‹2.334-16.991; p â€‹= â€‹0.009) and eHDM treatment (OR â€‹= â€‹0.741; 95%CI â€‹= â€‹0.129-0.917; p â€‹= â€‹0.007). CONCLUSION: The eHDM is an interesting and promising approach in the ARDS related to COVID-19 pneumonia, which reduces mortality, length of hospitalization and the need for mechanical ventilation.

Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir on Risk of Hospitalization Among Patients With COVID-19: The TOGETHER Randomized Clinical Trial.

Importance: Data on the efficacy of hydroxychloroquine or lopinavir-ritonavir for the treatment of high-risk outpatients with COVID-19 in developing countries are needed. Objective: To determine whether hydroxychloroquine or lopinavir-ritonavir reduces hospitalization among high-risk patients with early symptomatic COVID-19 in an outpatient setting. Design, Setting, and Participants: This randomized clinical trial was conducted in Brazil. Recently symptomatic adults diagnosed with respiratory symptoms from SARS-CoV-2 infection were enrolled between June 2 and September 30, 2020. The planned sample size was 1476 patients, with interim analyses planned after 500 patients were enrolled. The trial was stopped after the interim analysis for futility with a sample size of 685 patients. Statistical analysis was performed in December 2020. Interventions: Patients were randomly assigned to hydroxychloroquine (800 mg loading dose, then 400 mg daily for 9 days), lopinavir-ritonavir (loading dose of 800 mg and 200 mg, respectively, every 12 hours followed by 400 mg and 100 mg, respectively, every 12 hours for the next 9 days), or placebo. Main Outcomes and Measures: The primary outcomes were COVID-19-associated hospitalization and death assessed at 90 days after randomization. COVID-19-associated hospitalization was analyzed with a Cox proportional hazards model. The trial included the following secondary outcomes: all-cause hospitalization, viral clearance, symptom resolution, and adverse events. Results: Of 685 participants, 632 (92.3%) self-identified as mixed-race, 377 (55.0%) were women, and the median (range) age was 53 (18-94) years. A total of 214 participants were randomized to hydroxychloroquine; 244, lopinavir-ritonavir; and 227, placebo. At first interim analysis, the data safety monitoring board recommended stopping enrollment of both hydroxychloroquine and lopinavir-ritonavir groups because of futility. The proportion of patients hospitalized for COVID-19 was 3.7% (8 participants) in the hydroxychloroquine group, 5.7% (14 participants) in the lopinavir-ritonavir group, and 4.8% (11 participants) in the placebo group. We found no significant differences between interventions for COVID-19-associated hospitalization (hydroxychloroquine: hazard ratio [HR], 0.76 [95% CI, 0.30-1.88]; lopinavir-ritonavir: HR, 1.16 [95% CI, 0.53-2.56] as well as for the secondary outcome of viral clearance through day 14 (hydroxychloroquine: odds ratio [OR], 0.91 [95% CI, 0.82-1.02]; lopinavir-ritonavir: OR, 1.04 [95% CI, 0.94-1.16]). At the end of the trial, there were 3 fatalities recorded, 1 in the placebo group and 2 in the lopinavir-ritonavir intervention group. Conclusions and Relevance: In this randomized clinical trial, neither hydroxychloroquine nor lopinavir-ritonavir showed any significant benefit for decreasing COVID-19-associated hospitalization or other secondary clinical outcomes. This trial suggests that expedient clinical trials can be implemented in low-income settings even during the COVID-19 pandemic. Trial Registration: ClinicalTrials.gov Identifier: NCT04403100.

Anticoagulation Before Hospitalization Is a Potential Protective Factor for COVID-19: Insight From a French Multicenter Cohort Study.

Background Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with thrombotic outcomes with coagulation and endothelial disorders. Based on that, several anticoagulation guidelines have been proposed. We aimed to determine whether anticoagulation therapy modifies the risk of developing severe COVID-19. Methods and Results Patients with COVID-19 initially admitted in medical wards of 24 French hospitals were included prospectively from February 26 to April 20, 2020. We used a Poisson regression model, Cox proportional hazard model, and matched propensity score to assess the effect of anticoagulation on outcomes (intensive care unit admission or in-hospital mortality). The study enrolled 2878 patients with COVID-19, among whom 382 (13.2%) were treated with oral anticoagulation therapy before hospitalization. After adjustment, anticoagulation therapy before hospitalization was associated with a better prognosis with an adjusted hazard ratio of 0.70 (95% CI, 0.55-0.88). Analyses performed using propensity score matching confirmed that anticoagulation therapy before hospitalization was associated with a better prognosis, with an adjusted hazard ratio of 0.43 (95% CI, 0.29-0.63) for intensive care unit admission and adjusted hazard ratio of 0.76 (95% CI, 0.61-0.98) for composite criteria intensive care unit admission or death. In contrast, therapeutic or prophylactic low- or high-dose anticoagulation started during hospitalization were not associated with any of the outcomes. Conclusions Anticoagulation therapy used before hospitalization in medical wards was associated with a better prognosis in contrast with anticoagulation initiated during hospitalization. Anticoagulation therapy introduced in early disease could better prevent COVID-19-associated coagulopathy and endotheliopathy, and lead to a better prognosis.

Early versus deferred anti-SARS-CoV-2 convalescent plasma in patients admitted for COVID-19: A randomized phase II clinical trial.

BACKGROUND: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. METHODS AND FINDINGS: The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion. CONCLUSIONS: In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration. TRIAL REGISTRATION: NCT04375098.

Effects of non-drug interventions on depression, anxiety and sleep in COVID-19 patients: a systematic review and meta-analysis.

OBJECTIVE: Patients with Coronavirus Disease 2019 (COVID-19) suffer from anxiety, depression and sleep disorders due to isolation treatment, among other reasons. Whether non-drug interventions can be alternative therapies for COVID-19 patients with anxiety, depression and sleep disorders is controversial. Therefore, we conducted a meta-analysis and systematic review to evaluate the effects of non-drug interventions on anxiety, depression and sleep in patients with COVID-19 to provide guidance for clinical application. MATERIALS AND METHODS: We searched the following databases for randomized controlled trials (RCTs) from December 2019 to July 2020: China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chongqing VIP Chinese Science and Technology Periodical Database (VIP), Wanfang, Cochrane Library, Web of Science, PubMed, MEDLINE and Embase. Two investigators independently screened the literature according to the inclusion and exclusion criteria, extracted data and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.3 software. RESULTS: A total of 5 articles with 768 subjects were included. Meta-analysis results indicated that non-drug interventions can reduce anxiety [SMD=-1.40, 95% CI (-1.62, -1.17), p<0.00001] and depression [SMD=-1.22, 95% CI (-2.01, -0.43), p=0.002] scores in patients with COVID-19. Descriptive analysis indicated that non-drug interventions can improve the sleep status of COVID-19 patients. Sensitivity analysis indicated that the meta-analysis results were stable. Egger's test and Begg's test showed no publication bias. CONCLUSIONS: This meta-analysis found that non-drug interventions can reduce the anxiety and depression scores of patients with COVID-19. Due to the limitations of this study, more high-quality studies are needed to verify the findings, especially the effect of non-drug interventions on improving the sleep status of COVID-19 patients.

At-admission hyperglycemia is consistently associated with poor prognosis and early intervention can improve outcomes in patients with COVID-19.

BACKGROUND & AIMS: At-admission hyperglycemia have been associated with poorer outcome during critical illnesses. At-admission hyperglycemia in previously unknown diabetes is not uncommonly encountered entity in patients with COVID-19. We sought to find out the outcomes of at-admission hyperglycemia and effect of early intervention to achieve optimal glycemic control in relation to COVID-19 patients. METHODS: We searched the PubMed and Google Scholar database up till August 20, 2020 using specific keywords related to our aims and objectives. RESULTS: All currently available evidences clearly hint that at-admission hyperglycemia in patients with COVID-19 is associated with a poorer outcome, compared with normoglycemic individuals. Fortunately, early intervention by achieving an optimal glycemic control has also been associated with a significant improvement in the outcomes in patients with COVID-19. CONCLUSION: At-admission hyperglycemia should be taken seriously by all clinicians treating patients with COVID-19. All efforts should be made towards an optimal glycemic control in patients with COVID-19, even in absence of pre-existing diabetes.

Community interventions in Low-And Middle-Income Countries to inform COVID-19 control implementation decisions in Kenya: A rapid systematic review.

Globally, public health measures like face masks, hand hygiene and maintaining social distancing have been implemented to delay and reduce local transmission of COVID-19. To date there is emerging evidence to provide effectiveness and compliance to intervention measures on COVID-19 due to rapid spread of the disease. We synthesized evidence of community interventions and innovative practices to mitigate COVID-19 as well as previous respiratory outbreak infections which may share some aspects of transmission dynamics with COVID-19. In the study, we systematically searched the literature on community interventions to mitigate COVID-19, SARS (severe acute respiratory syndrome), H1N1 Influenza and MERS (middle east respiratory syndrome) epidemics in PubMed, Google Scholar, World Health Organization (WHO), MEDRXIV and Google from their inception until May 30, 2020 for up-to-date published and grey resources. We screened records, extracted data, and assessed risk of bias in duplicates. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study is registered with PROSPERO (CRD42020183064). Of 41,138 papers found, 17 studies met the inclusion criteria in various settings in Low- and Middle-Income Countries (LMICs). One of the papers from LMICs originated from Africa (Madagascar) with the rest from Asia 9 (China 5, Bangladesh 2, Thailand 2); South America 5 (Mexico 3, Peru 2) and Europe 2 (Serbia and Romania). Following five studies on the use of face masks, the risk of contracting SARS and Influenza was reduced OR 0.78 and 95% CI = 0.36-1.67. Equally, six studies on hand hygiene practices reported a reduced risk of contracting SARS and Influenza OR 0.95 and 95% CI = 0.83-1.08. Further two studies that looked at combined use of face masks and hand hygiene interventions showed the effectiveness in controlling the transmission of influenza OR 0.94 and 95% CI = 0.58-1.54. Nine studies on social distancing intervention demonstrated the importance of physical distance through closure of learning institutions on the transmission dynamics of disease. The evidence confirms the use of face masks, good hand hygiene and social distancing as community interventions are effective to control the spread of SARS and influenza in LMICs. However, the effectiveness of community interventions in LMICs should be informed by adherence of the mitigation measures and contextual factors taking into account the best practices. The study has shown gaps in adherence/compliance of the interventions, hence a need for robust intervention studies to better inform the evidence on compliance of the interventions. Nevertheless, this rapid review of currently best available evidence might inform interim guidance on similar respiratory infectious diseases like Covid-19 in Kenya and similar LMIC context.

Epidemiological and clinical based study on four passages of COVID-19 patients: intervention at asymptomatic period contributes to early recovery.

BACKGROUND: With the worldwide spread of the 2019 novel coronavirus, scarce knowledge is available on the clinical features of more than two passages of patients. Further, in China, early intervention policy has been enacted since February. Whether early intervention contributes to swift recovery is still unknown. Hence, in this study, we focused on the patients from an isolated area, investigated the epidemiological and clinical characteristics of four serial passages of the virus. METHODS: From January 25 to February 29, 2020, all patient data on the SARS-CoV-2 passages in this isolated area were traced, and the patients were grouped according to the passaging of SARS-CoV-2. Clinical characteristics of patients, including laboratory, radiology, treatment and outcomes, were collected and analyzed. RESULTS: A total of 78 patients with four passages of virus transmission were included in this study. One patient transmitted SARS-CoV-2 to 8 patients (passage 2, P2), who next infected 23 patients (passage 3, P3), and then 46 patients (passage 4, P4). P2 received antiviral treatment when they had symptom, whereas P4 received antiviral treatment during their asymptomatic period. The incubation periods for P2, P3 and P4 patients were 7 days (IQR:2-12), 8 days (IQR:4-13) and 10 days (IQR:7-15), respectively. P2 patients showed lymphocytopenia (0.79 × 109/L), decreased lymphocyte percentages (12.15%), increased white blood cell count (6.51 × 109/L), increased total bilirubin levels (25% of P2 patients), increased C-reactive protein levels (100% of P2 patients) and abnormal liver function. By chest CT scans, all P2 patients (100%), 15 of P3 patients (65.22%) and 16 of P4 patients (34.78%) showed abnormality with typical feature of ground glass opacity. All of P2 patients (100%) received oxygen therapy, and in contrast, 19 of P4 patients (41.3%) received oxygen therapy. Further, significant decreased nucleic acid positive periods was found in P4 group (16 days, IQR: 10-23), compared with that of P2 group (22 days, IQR: 16-27). Moreover, the severity ratios were sharply decreased from 50% (P2 patients) to 4.35% (P4 patients), and the case fatality rate is zero. CONCLUSIONS: Judged from four passages of patients, early intervention contributes to the early recovery of COVID-19 patients.

Low-impact social distancing interventions to mitigate local epidemics of SARS-CoV-2.

Many jurisdictions implemented intensive social distancing to suppress SARS-CoV-2 transmission. The challenge now is to mitigate the ongoing COVID-19 epidemic without overburdening economic and social activities. An agent-based model simulated the population of King County, Washington. SARS-CoV-2 transmission probabilities were estimated by fitting simulated to observed hospital admissions. Interventions considered included encouraging telecommuting, reducing contacts to high-risk persons, and reductions to contacts outside of the home, among others. Removing all existing interventions would result in nearly 42,000 COVID-19 hospitalizations between June 2020 and January 2021, with peak hospital occupancy exceeding available beds 6-fold. Combining interventions is predicted to reduce total hospitalizations by 48% (95% CI, 47-49%), with peak COVID-19 hospital occupancy of 70% of total beds. Targeted school closures can further reduce the peak occupancy. Combining low-impact interventions may mitigate the course of the COVID-19 epidemic, keeping hospital burden within the capacity of the healthcare system.

Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia.

BACKGROUND: Pneumonia with respiratory failure represents the main cause of death in COVID-19, where hyper inflammation plays an important role in lung damage. This study aims to evaluate if tocilizumab, an anti-soluble IL-6 receptor monoclonal antibody, reduces patients' mortality. METHODS: 85 consecutive patients admitted to the Montichiari Hospital (Italy) with COVID-19 related pneumonia and respiratory failure, not needing mechanical ventilation, were included if satisfying at least one among: respiratory rate ≥ 30 breaths/min, peripheral capillary oxygen saturation ≤ 93% or PaO2/FiO2<=300 mmHg. Patients admitted before March 13th (n=23) were prescribed the standard therapy (hydroxychloroquine, lopinavir and ritonavir) and were considered controls. On March 13th tocilizumab was available and patients admitted thereafter (n=62) received tocilizumab once within 4 days from admission, plus the standard care. RESULTS: Patients receiving tocilizumab showed significantly greater survival rate as compared to control patients (hazard ratio for death, 0.035; 95% confidence interval [CI], 0.004 to 0.347; p = 0.004), adjusting for baseline clinical characteristics. Two out of 62 patients of the tocilizumab group and 11 out of 23 in the control group died. 92% and 42.1% of the discharged patients in the tocilizumab and control group respectively, recovered. The respiratory function resulted improved in 64.8% of the observations in tocilizumab patients who were still hospitalized, whereas 100% of controls worsened and needed mechanical ventilation. No infections were reported. CONCLUSIONS: Tocilizumab results to have a positive impact if used early during Covid-19 pneumonia with severe respiratory syndrome in terms of increased survival and favorable clinical course.