Coronavirus COVID-19 Update for March 8, 2021

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Clinical Reports

Difference in SARS-CoV-2 attack rate between children and adults may reflect bias
The epidemiology of coronavirus disease 2019 (COVID-19) in children has been challenging to establish, owing to the high prevalence of asymptomatic infection in this population. Lower secondary attack rates in children compared to adults have been observed in household contact studies, but there is evidence this may reflect lower testing in children and reduced exposure, rather than a genuine difference in biological susceptibility. Additionally, children may shed infectious virus for a shorter period than adults and their antibody response may be less broad, with implications for both polymerase chain reaction and serological testing. Improvements in study design, data collection, and data interpretation are required to better understand the epidemiology of COVID-19 in children.
Update on long COVID prevalence estimate
The Coronavirus Infection Survey is a survey sample of respondents randomly selected from the UK population (excluding communal establishments) who are followed-up weekly for the first month from enrolment, followed by monthly for a up to a year. At each visit, respondents are swab tested for COVID-19 and describe their current symptoms (from a list of 12 common COVID-19 symptoms) to the interviewer. Time-to-symptom-discontinuation was estimated using survival analysis techniques. Discontinuation was defined as the first post-infection occurrence of the respondent not reporting any symptoms for two consecutive visits (that is, the visit defining the date of discontinuation plus the next one). To allow time from infection to symptom onset, symptoms were tracked from the first visit where the respondent tested positive for COVID-19 or within the next month. 22.1% (95% CI: 21.2% to 23.2%) of respondents were still reporting at least one symptom at 5 weeks following COVID-19 infection, while 9.8% (7.4% to 13.1%) had symptoms at 12 weeks. The most common symptoms at 5 weeks were fatigue (12.7%), cough (12.4%), headache (11.1%), loss of taste and/or smell (10.4%), and myalgia (8.8%). Females had a slightly higher 5-week prevalence than males, at 23.6% and 20.7%, respectively, while prevalence was greatest among those in the 35-49 years age group (26.8%), followed by 50-69 years (26.1%) and 25-34 years (24.9%)

Antiviral Therapeutics and Vaccines

Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19
To address the question, is treatment with convalescent plasma associated with improved clinical outcomes, authors conducted a meta-analysis of 4 peer-reviewed and published randomized clinical trials including 1060 patients with COVID-19 treated with convalescent plasma vs control. The risk ratio for mortality was 0.93 and after the addition of 6 unpublished randomized clinical trials and 10 722 patients, the risk ratio for mortality was 1.02; neither finding was statistically significant. No significant associations with benefit were shown for hospital length of stay, mechanical ventilation use, clinical improvement, or clinical deterioration. Among patients with COVID-19, treatment with convalescent plasma compared with control was not associated with improved survival or other positive clinical outcomes.
NIH halts trial of COVID-19 convalescent plasma in emergency department patients with mild symptoms
The National Institutes of Health has halted a clinical trial evaluating the safety and effectiveness of COVID-19 convalescent plasma in treating emergency department patients who developed mild to moderate symptoms of COVID-19, the disease caused by the coronavirus SARS-CoV-2. An independent data and safety monitoring board (DSMB) met on Feb. 25, 2021 for the second planned interim analysis of the trial data and determined that while the convalescent plasma intervention caused no harm, it was unlikely to benefit this group of patients. After the meeting, the DSMB recommended that the National Heart, Lung, and Blood Institute (NHLBI), part of NIH, stop enrolling new patients into the study. NHLBI did so immediately. COVID-19 convalescent plasma, also known as “survivor’s plasma,” contains antibodies, or special proteins, generated by the body’s immune system to the novel coronavirus. More than 100,000 people in the United States and many more worldwide have already been treated with it since the pandemic began.
Dexamethasone in Hospitalized Patients with Covid-19
In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, patients were randomly assigned to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.92 to 1.55). In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support.
Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia
In this phase 3 trial, patients who were hospitalized with severe Covid-19 pneumonia were randomly assigned in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants received a second dose of tocilizumab or placebo 8 to 24 hours after the first dose. The primary outcome was clinical status at day 28 on an ordinal scale ranging from 1 (discharged or ready for discharge) to 7 (death) in the modified intention-to-treat population, which included all the patients who had received at least one dose of tocilizumab or placebo. Of the 452 patients who underwent randomization, 438 (294 in the tocilizumab group and 144 in the placebo group) were included in the primary and secondary analyses. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% confidence interval [CI], 1.0 to 1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0 to 4.0) in the placebo group (between-group difference, −1.0; 95% CI, −2.5 to 0; P=0.31 by the van Elteren test). In the safety population, serious adverse events occurred in 103 of 295 patients (34.9%) in the tocilizumab group and in 55 of 143 patients (38.5%) in the placebo group. Mortality at day 28 was 19.7% in the tocilizumab group and 19.4% in the placebo group (weighted difference, 0.3 percentage points (95% CI, –7.6 to 8.2; nominal P=0.94). In this randomized trial involving hospitalized patients with severe Covid-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days.