Real-World Evidence of Neutralizing Monoclonal Antibodies for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

BACKGROUND: Neutralizing monoclonal antibodies (mAbs) were authorized for the treatment of COVID-19 outpatients based on clinical trials completed early in the pandemic, which were underpowered for mortality and subgroup analyses. Real-world data studies are promising for further assessing rapidly deployed therapeutics. RESEARCH QUESTION: Did mAb treatment prevent progression to severe disease and death across pandemic phases and based on risk factors, including prior vaccination status? STUDY DESIGN AND METHODS: This observational cohort study included nonhospitalized adult patients with SARS-CoV-2 infection from November 2020 to October 2021 using electronic health records from a statewide health system plus state-level vaccine and mortality data. Using propensity matching, we selected approximately 2.5 patients not receiving mAbs for each patient who received mAb treatment under emergency use authorization. The primary outcome was 28-day hospitalization; secondary outcomes included mortality and hospitalization severity. RESULTS: Of 36,077 patients with SARS-CoV-2 infection, 2,675 receiving mAbs were matched to 6,677 patients not receiving mAbs. Compared with mAb-untreated patients, mAb-treated patients had lower all-cause hospitalization (4.0% vs 7.7%; adjusted OR, 0.48; 95% CI, 0.38-0.60) and all-cause mortality (0.1% vs 0.9%; adjusted OR, 0.11; 95% CI, 0.03-0.29) to day 28; differences persisted to day 90. Among hospitalized patients, mAb-treated patients had shorter hospital length of stay (5.8 vs 8.5 days) and lower risk of mechanical ventilation (4.6% vs 16.6%). Results were similar for preventing hospitalizations during the Delta variant phase (adjusted OR, 0.35; 95% CI, 0.25-0.50) and across subgroups. Number-needed-to-treat (NNT) to prevent hospitalization was lower for subgroups with higher baseline risk of hospitalization; for example, multiple comorbidities (NNT = 17) and not fully vaccinated (NNT = 24) vs no comorbidities (NNT = 88) and fully vaccinated (NNT = 81). INTERPRETATION: Real-world data revealed a strong association between receipt of mAbs and reduced hospitalization and deaths among COVID-19 outpatients across pandemic phases. Real-world data studies should be used to guide practice and policy decisions, including allocation of scarce resources.

Real-world evaluation of bebtelovimab effectiveness during the period of COVID-19 Omicron variants, including BA.4/BA.5.

OBJECTIVES: Bebtelovimab is an anti-SARS-CoV-2 monoclonal antibody active against Omicron lineage variants authorized to treat high-risk outpatients with COVID-19. We sought to determine the real-world effectiveness of bebtelovimab during the Omicron phases BA.2/BA2.12.1/BA4/BA5. METHODS: We conducted a retrospective cohort study of adults with SARS-CoV-2 infection between April 6 and October 11, 2022, using health records linked to vaccine and mortality data. We used propensity scores to match of bebtelovimab-treated with untreated outpatients. The primary outcome was 28-day all-cause hospitalization. The secondary outcomes were 28-day COVID-19-related hospitalization, 28-day all-cause mortality, 28-day emergency department visits, maximum respiratory support level, intensive care unit admission, and in-hospital mortality among hospitalized patients. We used logistic regression to determine bebtelovimab treatment effectiveness. RESULTS: Among 22,720 patients with SARS-COV-2 infection, 3739 bebtelovimab-treated patients were matched to 5423 untreated patients. Compared with no treatment, bebtelovimab was associated with lower odds of 28-day all-cause hospitalization (1.3% vs 2.1%, adjusted odds ratio: 0.53; 95% confidence interval: 0.37-0.74, P <0.001), as well as COVID-19-related hospitalization (1.0% vs 2.0%, adjusted odds ratio: 0.44 [95% confidence interval: 0.30-0.64], P <0.001). Bebtelovimab appeared to be more beneficial in lowering the odds of hospitalization among patients with two or more comorbidities (interaction P = 0.03). CONCLUSION: During the Omicron BA.2/BA.2.12.1/BA.4/BA.5 variant phase, bebtelovimab was associated with lower hospitalization.

Real World Evidence of the Neutralizing Monoclonal Antibody Sotrovimab for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

BACKGROUND: It is not known whether sotrovimab, a neutralizing monoclonal antibody (mAb) treatment authorized for early symptomatic COVID-19 patients, is also effective in preventing the progression of severe disease and mortality following SARS-CoV-2 Delta variant infection. METHODS: Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from October 1st 2021 - December 11th 2021, using electronic health records from a statewide health system plus state-level vaccine and mortality data. We used propensity matching to select 3 patients not receiving mAbs for each patient who received outpatient sotrovimab treatment. The primary outcome was 28-day hospitalization; secondary outcomes included mortality and severity of hospitalization. RESULTS: Of 10,036 patients with SARS-CoV-2 infection, 522 receiving sotrovimab were matched to 1,563 not receiving mAbs. Compared to mAb-untreated patients, sotrovimab treatment was associated with a 63% decrease in the odds of all-cause hospitalization (raw rate 2.1% versus 5.7%; adjusted OR 0.37, 95% CI 0.19-0.66) and an 89% decrease in the odds of all-cause 28-day mortality (raw rate 0% versus 1.0%; adjusted OR 0.11, 95% CI 0.0-0.79), and may reduce respiratory disease severity among those hospitalized. CONCLUSION: Real-world evidence demonstrated sotrovimab effectiveness in reducing hospitalization and all-cause 28-day mortality among COVID-19 outpatients during the Delta variant phase.

Change in Effectiveness of Sotrovimab for Preventing Hospitalization and Mortality for At-risk COVID-19 Outpatients During an Omicron BA.1 and BA.1.1-Predominant Phase.

OBJECTIVES: Sotrovimab effectively prevented progression to severe disease and mortality following infection with pre-Omicron SARS-CoV-2 variants. We sought to determine whether sotrovimab is similarly effective against SARS-CoV-2 Omicron variant infection. METHODS: Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from December 26, 2021 to March 10, 2022, using electronic health records from a statewide health system. We propensity matching patients not receiving authorized treatment for each patient treated with sotrovimab. The primary outcome was 28-day hospitalization; secondary outcomes included mortality. We also propensity matched sotrovimab-treated patients from the Omicron and Delta phases. Logistic regression was used to determine sotrovimab effectiveness during Omicron and between variant phases. RESULTS: Of 30,247 SARS-CoV-2 Omicron variant infected outpatients, we matched 1,542 receiving sotrovimab to 3,663 not receiving treatment. Sotrovimab treatment was not associated with reduced odds of 28-day hospitalization (2.5% versus 3.2%; adjusted OR 0.82, 95% CI 0.55, 1.19) or mortality (0.1% versus 0.2%; adjusted OR 0.62, 95% CI 0.07, 2.78). Between phases, the observed treatment odds ratio was higher during Omicron than during Delta (OR 0.85 vs. 0.39, respectively; interaction p=0.053). CONCLUSIONS: Real-world evidence demonstrated sotrovimab was not associated with reduced 28-day hospitalization or mortality among COVID-19 outpatients during the Omicron BA.1 phase.

Real-world use of nirmatrelvir-ritonavir in outpatients with COVID-19 during the era of omicron variants including BA.4 and BA.5 in Colorado, USA: a retrospective cohort study.

BACKGROUND: Nirmatrelvir is a protease inhibitor with in-vitro activity against SARS-CoV-2, and ritonavir-boosted nirmatrelvir can reduce the risk of progression to severe COVID-19 among individuals at high risk infected with delta and early omicron variants. However, less is known about the effectiveness of nirmatrelvir-ritonavir during more recent BA.2, BA2.12.1, BA.4, and BA.5 omicron variant surges. We used our real-world data platform to evaluate the effect of nirmatrelvir-ritonavir treatment on 28-day hospitalisation, mortality, and emergency department visits among outpatients with early symptomatic COVID-19 during a SARS-CoV-2 omicron (BA.2, BA2.12.1, BA.4, and BA.5) predominant period in Colorado, USA. METHODS: We did a propensity-matched, retrospective, observational cohort study of non-hospitalised adult patients infected with SARS-CoV-2 between March 26 and Aug 25, 2022, using records from a statewide health system in Colorado. We obtained data from the electronic health records of University of Colorado Health, the largest health system in Colorado, with 13 hospitals and 141 000 annual hospital admissions, and with numerous ambulatory sites and affiliated pharmacies around the state. Included patients had a positive SARS-CoV-2 test or nirmatrelvir-ritonavir medication order. Exclusion criteria were an order for or administration of other SARS-CoV-2 treatments within 10 days of a positive SARS-CoV-2 test, hospitalisation at the time of positive SARS-CoV-2 test, and positive SARS-CoV-2 test more than 10 days before a nirmatrelvir-ritonavir order. We propensity score matched patients treated with nirmatrelvir-ritonavir with untreated patients. The primary outcome was 28-day all-cause hospitalisation. FINDINGS: Among 28 167 patients infected with SARS-CoV-2 between March 26 and Aug 25, 2022, 21 493 met the study inclusion criteria. 9881 patients received treatment with nirmatrelvir-ritonavir and 11 612 were untreated. Nirmatrelvir-ritonavir treatment was associated with reduced 28-day all-cause hospitalisation compared with no antiviral treatment (61 [0·9%] of 7168 patients vs 135 [1·4%] of 9361 patients, adjusted odds ratio (OR) 0·45 [95% CI 0·33-0·62]; p<0·0001). Nirmatrelvir-ritonavir treatment was also associated with reduced 28-day all-cause mortality (two [<0·1%] of 7168 patients vs 15 [0·2%] of 9361 patients; adjusted OR 0·15 [95% CI 0·03-0·50]; p=0·0010). Using subsequent emergency department visits as a surrogate for clinically significant relapse, we observed a decrease after nirmatrelvir-ritonavir treatment (283 [3·9%] of 7168 patients vs 437 [4·7%] of 9361 patients; adjusted OR 0·74 [95% CI 0·63-0·87]; p=0·0002). INTERPRETATION: Real-world evidence reported during a BA.2, BA2.12.1, BA.4, and BA.5 omicron surge showed an association between nirmatrelvir-ritonavir treatment and reduced 28-day all-cause hospitalisation, all-cause mortality, and visits to the emergency department. With results that are among the first to suggest effectiveness of nirmatrelvir-ritonavir for non-hospitalised patients during an omicron period inclusive of BA.4 and BA.5 subvariants, these data support nirmatrelvir-ritonavir as an ongoing first-line treatment for adults acutely infected with SARS-CoV-2. FUNDING: US National Institutes of Health.

Association between treatment failure and hospitalization after receipt of neutralizing monoclonal antibody treatment for COVID-19 outpatients.

BACKGROUND: Neutralizing monoclonal antibodies (mAbs) are highly effective in reducing hospitalization and mortality among early symptomatic COVID-19 patients in clinical trials and real-world data. While resistance to some mAbs has since emerged among new variants, characteristics associated with treatment failure of mAbs remain unknown. METHODS: This multicenter, observational cohort study included patients with COVID-19 who received mAb treatment between November 20, 2020, and December 9, 2021. We utilized electronic health records from a statewide health system plus state-level vaccine and mortality data. The primary outcome was mAb treatment failure, defined as hospitalization or death within 28 days of a positive SARS-CoV-2 test. RESULTS: COVID-19 mAb was administered to 7406 patients. Hospitalization within 28 days of positive SARS-CoV-2 test occurred in 258 (3.5%) of all patients who received mAb treatment. Ten patients (0.1%) died within 28 days, and all but one were hospitalized prior to death. Characteristics associated with treatment failure included having two or more comorbidities excluding obesity and immunocompromised status (adjusted odds ratio [OR] 3.71, 95% confidence interval [CI] 2.52-5.56), lack of SARS-CoV-2 vaccination (OR 2.73, 95% CI 2.01-3.77), non-Hispanic black race/ethnicity (OR 2.21, 95% CI 1.20-3.82), obesity (OR 1.79, 95% CI 1.36-2.34), one comorbidity (OR 1.68, 95% CI 1.11-2.57), age ≥ 65 years (OR 1.62, 95% CI 1.13-2.35), and male sex (OR 1.56, 95% CI 1.21-2.02). Immunocompromised status (none, mild, or moderate/severe), pandemic phase, and type of mAb received were not associated with treatment failure (all p > 0.05). CONCLUSIONS: Comorbidities, lack of prior SARS-CoV-2 vaccination, non-Hispanic black race/ethnicity, obesity, age ≥ 65 years, and male sex are associated with treatment failure of mAbs.

The impact of the COVID-19 pandemic on the career choice of medicine: A cross-sectional study amongst pre-medical students in Pakistan.

Background: The COVID-19 pandemic has significantly affected the lives of healthcare workers due to the frontline nature of their work. Their hard work and sacrifice have forged new perceptions of healthcare workers. These changes may potentially influence students' interest in medicine. This study explores how the COVID-19 pandemic has affected premedical students' decisions to pursue medicine as a career. Methods: A cross-sectional study using a self-designed online questionnaire was carried out amongst pre-medical students across Pakistan. Results: A total of 1695 students from 93 public and private schools filled in the survey. After the onset of the COVID-19 pandemic, significantly more pre-medical students want to pursue medicine (60.7%-62.9%) and less are unsure (20.2%-17%). Students are significantly more likely to be motivated to pursue medicine due to altruistic benefits to society (57% vs. 62.7%) and be deterred by the risk of contracting infections on duty (10%-14.6%). There is a minor but significant increase in the popularity of internal medicine (17.1%-18.9%), public health (4.1% vs. 5.7%), emergency medicine (3.8% vs. 5.7%), pediatrics (3.8% vs. 4.7%), and radiology (2.1% vs. 2.9%). Most pre-medical students felt that doctors routinely undergo physical and emotional turmoil (84%). Conclusions: Although awareness of hardships faced by medical professionals has increased, motivation to pursue medicine has grown. Through understanding trends in the motivations of students to pursue medicine, medical schools can accommodate the expectations of incoming students and reach out to potential applicants.

Predicting Development Of Critical Illness In Patients With Covid-19 Presenting To A Tertiary Care Hospital In A Developing Country.

BACKGROUND: With the increasing number of COVID-19 patients and limited resources available to accommodate them, there is a need for risk stratification tools to ensure better utilization of resources. METHODS: We conducted a retrospective observational cohort study in patients discharged from the COVID designated areas of a large tertiary care hospital in Karachi, Pakistan from the 1st of May to the 31st of July, 2020. 581 patients were included and the COVID GRAM score was calculated at the time of admission and patients developing critical disease as per COVID GRAM study criteria (need of intensive care unit admission, invasive ventilation or death) after 24 hours of admission were noted. RESULTS: The mean age of the study population was 56.3±14.8 years. Patients that developed critical illness (as per COVID GRAM study criteria) beyond 24 hours after admission had higher COVID GRAM scores at admission versus those that did not (183.2±80.7 versus 130.3±42.6). The Area under the Receiver Operator Curve for the COVID gram score to predict critical illness in the study population was 0.802 (95% confidence interval, 0.753-0.850). On binary logistic multivariable regression analysis, the COVID GRAM and SOFA scores on admission and need of ICU admission during hospitalization were significant predictors of mortality 24 hours after admission. CONCLUSIONS: The COVID GRAM score is a useful risk assessment tool and can be used for appropriate allocation and prioritization of resources where they are most needed.

Development of Evidence-Based COVID-19 Management Guidelines for Local Context: The Methodological Challenges.

Background: The coronavirus disease 2019 (COVID-19) pandemic has presented as a therapeutic challenge for clinicians worldwide due to its rapid spread along with evolving evidence and understanding of the disease. Internationally, recommendations to guide the management of COVID-19 have been created and updated continuously by the WHO and CDC, which have been locally adapted by different countries. Similarly, Pakistan's National Command Operation Center (NCOC), in its national COVID-19 management strategy, generated guidelines for national implementation. Keeping the guidelines updated has proved challenging globally and locally. Here, we present a summary of the process to assess the evidence, including a time-restricted systematic review based on NCOC Clinical Management Guidelines for COVID-19 Infections v4 published on 11th December 2020 version, correlating it with current recommendations and with input one of the guidelines authors, particularly noting the methodological challenges. Methods: We conducted a systematic review synthesizing global research on treatment options for COVID-19 hospitalized patients, limiting it to pharmacological interventions for hospitalized COVID-19 patients included in Pakistan's NCOC's national guidelines v4 published on 11th December 2020. Each treatment recommendation's strength and quality of evidence was assessed based on the grading of recommendations assessment, development, and evaluation (GRADE) methodology. These were then compared to the most current living WHO COVID-19 pharmacological treatment guidelines v7.1. One of the authors of the NCOC guidelines reviewed and commented on the findings as well. Results: We note that the data from our systematic review strongly supports corticosteroids use in treating severe and critically ill COVID-19 hospitalized patients correlating with WHO v7.1 guidelines 24 September 2021. However, evidence from our review and WHO v7.1 for the use of tocilizumab had some conflicting evidence, with data from our review until December 2020 supporting only a weak recommendation for its use, compared to the strong recommendation by the WHO for the use of tocilizumab in patients with severe or critical COVID-19 infection. Regarding the use of antibiotics and ivermectin use in treating COVID-19 hospitalized patients, data from our review and WHO v 7.1 recommend against their use. Conclusion: Research data about the efficacy and safety of pharmacological interventions to treat hospitalized patients with COVID-19 are rapidly evolving, and based on it, the evidence for or against recommendations changes accordingly. Our study illustrates the challenges of keeping up with the evidence; the recommendations were based on studies up till December 2021, and we have compared our recommendations with the WHO v7.1, which showed some significant changes in the use of pharmacological treatment options.

Correlation Of Computerized Tomography (CT) Severity Score For COVID-19 Pneumonia With Clinical Outcomes.

BACKGROUND: Though various computerized tomography (CT) severity scores have been described for risk prognostication for coronavirus disease 2019 (COVID-19), most are challenging to calculate and have variable inter-observer agreement. The objective of this study was to develop a simple CT severity score (CT-SS) with good inter-observer agreement and assess its correlation with clinical outcome. METHODS: This retrospective study was conducted at the Aga Khan University Hospital (AKUH), from April-August 2020. All patients who were PCR positive for COVID-19 and underwent CT chest examination at AKUH were included. Severity of disease was described on the basis of a 10-point CT severity score (CT-SS) devised at our institution. CT-SS were categorized as Low (0-7) and High (8-10). Inter-observer reliability between radiologist and COVID-19 intensivist was assessed using the Kappa statistic. RESULTS: A total of 73 patients were included, the majority male (58.9%) with mean age 55.8±13.93 years. The CT-SS rated on 0-10 showed substantial inter-observer reliability between radiologist and intensivist with a Kappa statistic of 0.78. Patients with CT-SS 8-10 had a significantly higher ICU admission & intubation rate (53.8% vs. 23.5%) and mortality rate (35.9% vs. 11.8%; p=0.017), as compared to those with CT-SS 0-7. CONCLUSIONS: We conclude that the described CT severity score (CT-SS) is a quick, effective, and easily reproducible tool for prediction of adverse clinical outcome in patients with COVID 19 pneumonia. The tool shows good inter-observer agreement when calculated by radiologist and physician independently.

Acute Upper Airway Disease in Children With the Omicron (B.1.1.529) Variant of SARS-CoV-2-A Report From the US National COVID Cohort Collaborative.

This cohort study uses data from the US National COVID Cohort Collaborative to evaluate upper airway infections in children during the surge of the Omicron (B.1.1.529) variant of SARS-CoV-2 in the US.

A Review of Coronaviruses Associated With Kawasaki Disease: Possible Implications for Pathogenesis of the Multisystem Inflammatory Syndrome Associated With COVID-19.

Multisystem Inflammatory Syndrome in Children (MIS-C), representing a new entity in the spectrum of manifestations of COVID-19, bears symptomatic resemblance with Kawasaki Disease (KD). This review explores the possible associations between KD and the human coronaviruses and discusses the pathophysiological similarities between KD and MIS-C and proposes implications for the pathogenesis of MIS-C in COVID-19. Since 2005, when a case-control study demonstrated the association of a strain of human coronavirus with KD, several studies have provided evidence regarding the association of different strains of the human coronaviruses with KD. Thus, the emergence of the KD-like disease MIS-C in COVID-19 may not be an unprecedented phenomenon. KD and MIS-C share a range of similarities in pathophysiology and possibly even genetics. Both share features of a cytokine storm, leading to a systemic inflammatory response and oxidative stress that may cause vasculitis and precipitate multi-organ failure. Moreover, antibody-dependent enhancement, a phenomenon demonstrated in previous coronaviruses, and the possible superantigenic behavior of SARS-CoV-2, possibly may also contribute toward the pathogenesis of MIS-C. Lastly, there is some evidence of complement-mediated microvascular injury in COVID-19, as well as of endotheliitis. Genetics may also represent a possible link between MIS-C and KD, with variations in FcγRII and IL-6 genes potentially increasing susceptibility to both conditions. Early detection and treatment are essential for the management of MIS-C in COVID-19. By highlighting the potential pathophysiological mechanisms that contribute to MIS-C, our review holds important implications for diagnostics, management, and further research of this rare manifestation of COVID-19.

Specialized interferon action in COVID-19.

The impacts of interferon (IFN) signaling on COVID-19 pathology are multiple, with both protective and harmful effects being documented. We report here a multiomics investigation of systemic IFN signaling in hospitalized COVID-19 patients, defining the multiomics biosignatures associated with varying levels of 12 different type I, II, and III IFNs. The antiviral transcriptional response in circulating immune cells is strongly associated with a specific subset of IFNs, most prominently IFNA2 and IFNG. In contrast, proteomics signatures indicative of endothelial damage and platelet activation associate with high levels of IFNB1 and IFNA6. Seroconversion and time since hospitalization associate with a significant decrease in a specific subset of IFNs. Additionally, differential IFN subtype production is linked to distinct constellations of circulating myeloid and lymphoid immune cell types. Each IFN has a unique metabolic signature, with IFNG being the most associated with activation of the kynurenine pathway. IFNs also show differential relationships with clinical markers of poor prognosis and disease severity. For example, whereas IFNG has the strongest association with C-reactive protein and other immune markers of poor prognosis, IFNB1 associates with increased neutrophil to lymphocyte ratio, a marker of late severe disease. Altogether, these results reveal specialized IFN action in COVID-19, with potential diagnostic and therapeutic implications.

Residual symptoms and the quality of life in individuals recovered from COVID-19 infection: A survey from Pakistan.

BACKGROUND: There remains scarcity of literature regarding the patient's health status post-COVID-19 infection. This study analyzes the prevalence of residual symptoms and quality of life (QoL) after COVID-19. METHODS: An anonymous online survey was administrated in Pakistan from November 2020 to April 2021 in COVID-19 survivors. The questionnaire used the 12-Item Short Form Health Survey (SF-12) to assess mental and physical QoL. Multivariate linear regression was used to explore factors associated with mental and physical QoL scores. RESULTS: A total of 331 COVID-19 survivors participated in our survey. Around 42.0% of the cohort reported within 1-3 months of diagnosis of COVID-19. The common residual symptoms were body aches (39.9%), low mood (32.6%), and cough (30.2%). Better physical QoL was associated with being male (adjusted beta: 3.328) and having no residual symptoms (6.955). However, suffering from nausea/vomiting during initial COVID-19 infection (-4.026), being admitted to the ICU during COVID-19 infection (-9.164), and suffering from residual body aches (-5.209) and low mood (-2.959) was associated with poorer QoL. Better mental QoL was associated with being asymptomatic during initial COVID-19 infection (6.149) and post-COVID (6.685), while experiencing low mood post-COVID was associated with poorer mental QoL (-8.253 [-10.914, -5.592]). CONCLUSION: Despite presumed "recovery" from COVID-19, patients still face a wide range of residual symptoms months after initial infection, which contributes towards poorer QoL. Healthcare professionals must remain alert to the long-lasting effects of COVID-19 infection and aim to address them appropriately to improve patients' QoL.

Characteristics, Outcomes, and Severity Risk Factors Associated With SARS-CoV-2 Infection Among Children in the US National COVID Cohort Collaborative.

Importance: Understanding of SARS-CoV-2 infection in US children has been limited by the lack of large, multicenter studies with granular data. Objective: To examine the characteristics, changes over time, outcomes, and severity risk factors of children with SARS-CoV-2 within the National COVID Cohort Collaborative (N3C). Design, Setting, and Participants: A prospective cohort study of encounters with end dates before September 24, 2021, was conducted at 56 N3C facilities throughout the US. Participants included children younger than 19 years at initial SARS-CoV-2 testing. Main Outcomes and Measures: Case incidence and severity over time, demographic and comorbidity severity risk factors, vital sign and laboratory trajectories, clinical outcomes, and acute COVID-19 vs multisystem inflammatory syndrome in children (MIS-C), and Delta vs pre-Delta variant differences for children with SARS-CoV-2. Results: A total of 1 068 410 children were tested for SARS-CoV-2 and 167 262 test results (15.6%) were positive (82 882 [49.6%] girls; median age, 11.9 [IQR, 6.0-16.1] years). Among the 10 245 children (6.1%) who were hospitalized, 1423 (13.9%) met the criteria for severe disease: mechanical ventilation (796 [7.8%]), vasopressor-inotropic support (868 [8.5%]), extracorporeal membrane oxygenation (42 [0.4%]), or death (131 [1.3%]). Male sex (odds ratio [OR], 1.37; 95% CI, 1.21-1.56), Black/African American race (OR, 1.25; 95% CI, 1.06-1.47), obesity (OR, 1.19; 95% CI, 1.01-1.41), and several pediatric complex chronic condition (PCCC) subcategories were associated with higher severity disease. Vital signs and many laboratory test values from the day of admission were predictive of peak disease severity. Variables associated with increased odds for MIS-C vs acute COVID-19 included male sex (OR, 1.59; 95% CI, 1.33-1.90), Black/African American race (OR, 1.44; 95% CI, 1.17-1.77), younger than 12 years (OR, 1.81; 95% CI, 1.51-2.18), obesity (OR, 1.76; 95% CI, 1.40-2.22), and not having a pediatric complex chronic condition (OR, 0.72; 95% CI, 0.65-0.80). The children with MIS-C had a more inflammatory laboratory profile and severe clinical phenotype, with higher rates of invasive ventilation (117 of 707 [16.5%] vs 514 of 8241 [6.2%]; P < .001) and need for vasoactive-inotropic support (191 of 707 [27.0%] vs 426 of 8241 [5.2%]; P < .001) compared with those who had acute COVID-19. Comparing children during the Delta vs pre-Delta eras, there was no significant change in hospitalization rate (1738 [6.0%] vs 8507 [6.2%]; P = .18) and lower odds for severe disease (179 [10.3%] vs 1242 [14.6%]) (decreased by a factor of 0.67; 95% CI, 0.57-0.79; P < .001). Conclusions and Relevance: In this cohort study of US children with SARS-CoV-2, there were observed differences in demographic characteristics, preexisting comorbidities, and initial vital sign and laboratory values between severity subgroups. Taken together, these results suggest that early identification of children likely to progress to severe disease could be achieved using readily available data elements from the day of admission. Further work is needed to translate this knowledge into improved outcomes.

CHARACTERISTICS AND OUTCOMES OF 728,047 CHILDREN IN THE NATIONAL COVID COHORT COLLABORATIVE (N3C)

B Introduction: b SARS-CoV-2 can cause severe pediatric disease via acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C). Outcomes included case incidence and severity over time, risk factors for higher severity disease, vital sign and lab trajectories, clinical outcomes, and acute COVID-19 vs. We sought to determine the characteristics, changes over time, outcomes, and severity risk factors of SARS-CoV-2 infected children within the National COVID Cohort Collaborative (N3C). [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Low-cost peer-taught virtual research workshops for medical students in Pakistan: a creative, scalable, and sustainable solution for student research.

BACKGROUND: Pakistan has not been a major contributor to medical research, mainly because of the lack of learning opportunities to medical students. With the increase in online learning systems during COVID-19, research related skills can be taught to medical students via low-cost peer taught virtual research workshops. AIM OF THE STUDY: To assess the effectiveness of a comprehensive low-cost peer-taught virtual research workshops amongst medical students in Pakistan. METHODS: This quasi-experimental study assessed the effectiveness of five virtual research workshops (RWs) in improving core research skills. RWs for medical students from across Pakistan were conducted over Zoom by medical students (peer-teachers) at the Aga Khan University, Pakistan, with minimal associated costs. The content of the workshops included types of research, ethical approval and research protocols, data collection and analysis, manuscript writing, and improving networking skills for research. Improvement was assessed via pre-and post-quizzes for each RW, self-efficacy scores across 16 domains, and feedback forms. Minimum criteria for completion of the RW series was attending at least 4/5 RWs and filling the post-RW series feedback form. A 6-month post-RW series follow-up survey was also emailed to the participants. RESULTS: Four hundred medical students from 36 (/117; 30.8%) different medical colleges in Pakistan were enrolled in the RWs. However, only 307/400 (76.75%) medical students met the minimum requirement for completion of the RW series. 56.4% of the participants belonged to the pre-clinical years while the rest were currently to clinical years. The cohort demonstrated significant improvement in pre-and post-quiz scores for all 5 RWs (p <  0.001) with the greatest improvement in Data Collection and Analysis (+ 34.65%), and in self-efficacy scores across all domains (p <  0.001). 166/307 (54.1%) participants responded to the 6 months post-RWs follow-up survey. Compared to pre-RWs, Research involvement increased from 40.4 to 62.8% (p <  0.001) while proportion of participants with peer-reviewed publications increased from 8.4 to 15.8% (p = 0.043). CONCLUSION: Virtual RWs allow for a wide outreach while effectively improving research-related knowledge and skills, with minimal associated costs. In lower-middle-income countries, virtual RWs are a creative and cost-effective use of web-based technologies to facilitate medical students to contribute to the local and global healthcare research community.