Factors that predict severity of infection and seroconversion in immunocompromised children and adolescents with COVID-19 infection.

Objectives: We aimed to study the outcomes, severity, and seroconversion post SARS-CoV-2 infection in immunocompromised children and adolescents treated at our center. Method: For this observational study, all pediatric patients who had COVID-19 infection from Sep-22-2020 to Nov-10-2021were identified by reviewing our laboratory records. Their charts were reviewed to determine clinical severity and outcome. Blood samples were drawn for anti-SARS-CoV-2 antibody assay. Serious COVID-19 infection (SVI) was defined if the patient had moderate, severe, or critical illness. A cutoff of 100 U/mL anti-SARS-CoV-2 antibodies was used to categorize low and high titer seroconversion. Results: We identified 263 pediatric patients with COVID-19; most (68%) were symptomatic: 5% had severe or critical infection, 25% were hospitalized, 12 required respiratory support, 12 were admitted to the ICU, and five patients (2%) died. Multivariable analysis revealed several factors that predict SVI: Age above 12 years (p=0.035), body mass index above 95th percentile (p=0.034), comorbid conditions (p=0.025), absolute neutrophil count ≤500(p=0.014) and absolute lymphocyte count ≤300 (p=0.022). Levels of anti-SARS-CoV-2 spike antibodies were obtained for 173 patients at a median of 94 days (range, 14-300) after PCR diagnosis; of them 142 (82%) patients seroconverted; the lowest seroconversion rate was observed in patients with hematological malignancies (79%). Our univariable model showed that the following factors were predictive of low titer: lower ANC, p=0.01; hematologic malignancy, p=0.023; receiving steroids in the last 14 days, p=0.032; time since last chemotherapy or immunosuppressive therapy less than 30 days, p=0.002; and being on active chemotherapy in the last 3 months prior to infection, p<0.001. Conclusions: SARS-CoV-2 antibodies developed in most immunocompromised patients with COVID-19 infection in our study. Mortality was relatively low in our patients. Our univariable and multivariable models showed multiple variables that predict severity of infections and antibody response post COVID-19 infection. These observations may guide choice of active therapy during infection and the best timing of vaccination in this high-risk population.

Factors that predict severity of infection and seroconversion in immunocompromised children and adolescents with COVID-19 infection

Objectives We aimed to study the outcomes, severity, and seroconversion post SARS-CoV-2 infection in immunocompromised children and adolescents treated at our center. Method For this observational study, all pediatric patients who had COVID-19 infection from Sep-22-2020 to Nov-10-2021were identified by reviewing our laboratory records. Their charts were reviewed to determine clinical severity and outcome. Blood samples were drawn for anti-SARS-CoV-2 antibody assay. Serious COVID-19 infection (SVI) was defined if the patient had moderate, severe, or critical illness. A cutoff of 100 U/mL anti-SARS-CoV-2 antibodies was used to categorize low and high titer seroconversion. Results We identified 263 pediatric patients with COVID-19;most (68%) were symptomatic: 5% had severe or critical infection, 25% were hospitalized, 12 required respiratory support, 12 were admitted to the ICU, and five patients (2%) died. Multivariable analysis revealed several factors that predict SVI: Age above 12 years (p=0.035), body mass index above 95th percentile (p=0.034), comorbid conditions (p=0.025), absolute neutrophil count ≤500(p=0.014) and absolute lymphocyte count ≤300 (p=0.022). Levels of anti-SARS-CoV-2 spike antibodies were obtained for 173 patients at a median of 94 days (range, 14–300) after PCR diagnosis;of them 142 (82%) patients seroconverted;the lowest seroconversion rate was observed in patients with hematological malignancies (79%). Our univariable model showed that the following factors were predictive of low titer: lower ANC, p=0.01;hematologic malignancy, p=0.023;receiving steroids in the last 14 days, p=0.032;time since last chemotherapy or immunosuppressive therapy less than 30 days, p=0.002;and being on active chemotherapy in the last 3 months prior to infection, p<0.001. Conclusions SARS-CoV-2 antibodies developed in most immunocompromised patients with COVID-19 infection in our study. Mortality was relatively low in our patients. Our univariable and multivariable models showed multiple variables that predict severity of infections and antibody response post COVID-19 infection. These observations may guide choice of active therapy during infection and the best timing of vaccination in this high-risk population.

Obstacles and Considerations Related to Clinical Trial Research During the COVID-19 Pandemic.

The response to the COVID-19 pandemic from the research and science community has been vigorous, with information being released faster than that of any other event in human history. Articles related to the virus were being rapidly published by January 2020. A small fraction of these publications comprised reports of prospective clinical trials (0.25%), and many of these trials have imparted conflicting conclusions, leading to confusion among the public and the scientific community. Additionally, the pandemic has raised many serious scientific and ethical concerns related to clinical research. In this review, we divided the conduct of clinical research trials into three steps and critically reviewed each step, along with the challenges and obstacles arising amid the ongoing crisis. The clinical research steps we reviewed include (1) clinical trial design factors such as social and scientific value, feasibility, single vs. multicenter trials, randomization, control groups, endpoints, off-label and compassionate use of medications, data analysis, and verifying the integrity of data; (2) ethical issues such as committee approvals, efficiency, virtual visits and remote monitoring, informed consent, shipping investigational products, and external monitoring and audits; and (3) publication and sharing of preprints, press releases, social media, and misinformation. The COVID-19 pandemic is adversely affecting existing clinical trials for other ailments and diseases, including cancer, with most trials being delayed or deferred. Although urgency is needed to communicate effective treatment and prevention strategies for COVID-19, research efforts should maintain the same high-quality core ethical principles that governed human subject research before the pandemic. Despite the catastrophic devastation caused by the pandemic, the adoption of more flexible, cost-effective methods of conducting clinical trials (without compromising ethical conduct, safety, or data integrity, while maintaining research efficiency) represents a potential silver lining. Streamlining clinical research will help to congruently address other important health issues, despite the ongoing COVID-19 crisis.