Coronavirus COVID-19 Update for April 11, 2021

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Clinical Reports

Children and COVID19: State Level Data Report
State-level reports are the best publicly available and timely data on child COVID-19 cases in the United States. The American Academy of Pediatrics and the Children’s Hospital Association are collaborating to collect and share all publicly available data from states on child COVID-19 cases. The definition of “child” case is based on varying age ranges reported across states (see report Appendix for details and links to all data sources). COVID-19 cases among US children have reached the highest case count ever reported since the start of the pandemic. For the week ending December 30th, over 325,000 child COVID-19 cases were reported. This number is a 64% increase over the 199,000 added cases reported the week ending December 23rd and an almost doubling of case counts from the two weeks prior. Nearly 7.9 million children have tested positive for COVID-19 since the onset of the pandemic, representing over 1 in 10 US children. For the 21st week in a row child COVID-19 cases are above 100,000. Since the first week of September, there have been over 2.8 million additional child cases.
Placental Tissue Destruction and Insufficiency from COVID-19 Causes Stillbirth and Neonatal Death from Hypoxic-Ischemic Injury: A Study of 68 Cases with SARS-CoV-2 Placentitis from 12 Countries
Study researchers evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for SARS-CoV-2. This was a case-based retrospective clinico-pathological analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. Researchers found all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis, the three findings constituting SARS-CoV-2 placentitis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25/68) and chronic villitis (32%; 22/68). The majority (19, 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.
Thromboprophylaxis in Patients with COVID-19. A Brief Update to the CHEST Guideline and Expert Panel Report
Patients hospitalized with COVID-19 often exhibit markers of a hypercoagulable state and have an increased incidence of VTE. In response, CHEST issued rapid clinical guidance regarding prevention of VTE. Over the past 18 months the quality of the evidence has improved. Researchers thus sought to incorporate this evidence and update the recommendations as necessary. The update focuses on the optimal approach to thromboprophylaxis in hospitalized patients. Eight randomized controlled trials and one observational study were included. Meta-analysis, using a random effects model, was performed. We provide separate guidance statements for VTE prevention for acutely (moderately) ill hospitalized patients and critically ill patients in the ICU. However, we divided each original question and resulting recommendation into two questions: standard prophylaxis vs therapeutic (or escalated dose) prophylaxis and standard prophylaxis vs intermediate dose prophylaxis. This led to a change in one recommendation, and an upgrading of three additional recommendations based upon higher quality evidence. In conclusion, advances in care for patients with COVID-19 have improved overall outcomes. Despite this, rates of VTE in these patients remain elevated. Critically ill patients should receive standard thromboprophylaxis for VTE, and moderately ill patients with a low bleeding risk might benefit from therapeutic heparin. We see no role for intermediate dose thromboprophylaxis in either setting.
Azithromycin in patients with COVID-19: a systematic review and meta-analysis
Azithromycin has been widely used in the management of COVID-19. However, the evidence on its actual effects remains disperse and difficult to apply in clinical settings. This systematic review and meta-analysis summarizes the available evidence to date on the beneficial and adverse effects of azithromycin in patients with COVID-19. The PRISMA 2020 statement criteria was followed. Randomized controlled trials (RCTs) and observational studies comparing clinical outcomes of patients treated with and without azithromycin, indexed until 5 July 2021, were searched in PubMed, Embase, The Web of Science, Scopus, The Cochrane Central Register of Controlled Trials and MedRXivs. Researchers used random-effects models to estimate pooled effect size from aggregate data. The initial search produced 4950 results. Finally, 16 studies, 5 RCTs and 11 with an observational design, with a total of 22 984 patients, were included. The meta-analysis showed no difference in mortality for those treated with or without azithromycin, in observational studies [OR: 0.90 (0.66-1.24)], RCTs [OR: 0.97 (0.87-1.08)] and also when both types of studies were pooled together [with an overall OR: 0.95 (0.79-1.13)]. Different individual studies also reported no significant difference for those treated with or without azithromycin in need for hospital admission or time to admission from ambulatory settings, clinical severity, need for intensive care, or adverse effects. The results presented in this systematic review do not support the use of azithromycin in the management of COVID-19.

Antiviral Therapeutics and Vaccines

Effectiveness of Maternal Vaccination with mRNA COVID-19 Vaccine During Pregnancy Against COVID-19–Associated Hospitalization in Infants Aged <6 Months — 17 States, July 2021–January 2022
COVID-19 vaccination during pregnancy is recommended to prevent severe illness and death in pregnant women. Infants are at risk for COVID-19–associated complications, including respiratory failure and other life-threatening complications. Effectiveness of maternal completion of a 2-dose primary mRNA COVID-19 vaccination series during pregnancy against COVID-19 hospitalization among infants aged <6 months was 61% (95% CI = 31% to 78%). Effectiveness of completion of the primary COVID-19 vaccine series early and later in pregnancy was 32% (95% CI = –43% to 68%) and 80% (95% CI = 55% to 91%), respectively. Completion of a 2-dose mRNA COVID-19 vaccination series during pregnancy might help prevent COVID-19 hospitalization among infants aged <6 months.
Safety Monitoring of COVID-19 Vaccine Booster Doses Among Adults — United States, September 22, 2021–February 6, 2022
In preauthorization trials, adverse reactions were reported less frequently following a homologous COVID-19 mRNA vaccine booster dose than after receipt of the second primary dose. In this report, review of surveillance data found that local and systemic reactions were less frequent after a homologous COVID-19 mRNA vaccine booster dose than after the second primary vaccine dose. Myocarditis was rarely reported following an mRNA vaccine booster dose. All persons aged ≥12 years should receive a COVID-19 booster dose. Vaccination providers should educate patients that local and systemic reactions are expected following a homologous COVID-19 mRNA vaccine booster; however, these reactions are less common than those following the second primary series dose.
Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19
Researchers conducted a phase 2–3 double-blind, randomized, controlled trial in which symptomatic, unvaccinated, nonhospitalized adults at high risk for progression to severe coronavirus disease 2019 (Covid-19) were assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir (a pharmacokinetic enhancer) or placebo every 12 hours for 5 days. Covid-19–related hospitalization or death from any cause through day 28, viral load, and safety were evaluated. A total of 2246 patients underwent randomization; 1120 patients received nirmatrelvir plus ritonavir (nirmatrelvir group) and 1126 received placebo (placebo group). In the planned interim analysis of patients treated within 3 days after symptom onset (modified intention-to-treat population, comprising 774 of the 1361 patients in the full analysis population), the incidence of Covid-19–related hospitalization or death by day 28 was lower in the nirmatrelvir group than in the placebo group by 6.32 percentage points (95% confidence interval [CI], −9.04 to −3.59; P<0.001; relative risk reduction, 89.1%); the incidence was 0.77% (3 of 389 patients) in the nirmatrelvir group, with 0 deaths, as compared with 7.01% (27 of 385 patients) in the placebo group, with 7 deaths. Efficacy was maintained in the final analysis involving the 1379 patients in the modified intention-to-treat population, with a difference of −5.81 percentage points (95% CI, −7.78 to −3.84; P<0.001; relative risk reduction, 88.9%). All 13 deaths occurred in the placebo group. Treatment of symptomatic Covid-19 with nirmatrelvir plus ritonavir resulted in a risk of progression to severe Covid-19 that was 89% lower than the risk with placebo, without evident safety concerns.
FDA Authorizes New Monoclonal Antibody for Treatment of COVID-19
Today, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for a new monoclonal antibody for the treatment of COVID-19 that retains activity against the omicron variant. The EUA for bebtelovimab is for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kilograms, which is about 88 pounds) with a positive COVID-19 test, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options approved or authorized by the FDA are not accessible or clinically appropriate.
Interleukin-1 blocking agents for treating COVID-19
Interleukin-1 (IL-1) blocking agents have been used for treating severe coronavirus disease 2019 (COVID-19), on the premise that their immunomodulatory effect might be beneficial in people with COVID-19. Study authors assessed the effects of IL-1 blocking agents compared with standard care alone or with placebo on effectiveness and safety outcomes in people with COVID-19. They included randomized controlled trials (RCTs) evaluating IL-1 blocking agents compared with standard care alone or with placebo for people with COVID-19, regardless of disease severity. Two researchers independently screened and extracted data and assessed the risk of bias with the Cochrane Risk of Bias 2 tool. Overall, researchers did not find evidence for an important beneficial effect of IL-1 blocking agents. The evidence is uncertain or very uncertain for several outcomes. Sixteen trials of anakinra and canakinumab with no results are currently registered, of which four are completed, and four terminated.
Antibody Evasion Properties of SARS-CoV-2 Omicron Sublineages
Current findings indicate that these three sublineages of Omicron are antigenically equidistant from the wild-type SARS-CoV-2 and thus similarly threaten the efficacies of current vaccines. BA.2 also exhibited marked resistance to 17 of 19 neutralizing monoclonal antibodies tested, including S309 (sotrovimab), which had retained appreciable activity against BA.1 and BA.1+R346K. This new finding shows that no presently approved or authorized monoclonal antibody therapy could adequately cover all sublineages of the Omicron variant.
The effectiveness of vaccination against long COVID: A rapid evidence briefing
There is evidence that vaccinated people who are subsequently infected with COVID-19 are less likely to report symptoms of long COVID than unvaccinated people, in the short term (4 weeks after infection), medium-term (12 to 20 weeks after infection), and long term (6 months after infection). This is in addition to any benefit of vaccination in preventing COVID-19 infection (5). There is also evidence that unvaccinated people with long COVID who were subsequently vaccinated had, on average, reduced long COVID symptoms (though some people reported worsened symptoms after vaccination). Additionally, there was evidence that unvaccinated people with long COVID who were subsequently vaccinated reported fewer long COVID symptoms than those who remained unvaccinated. However, there is a risk of bias across all studies due to differences in people who were vaccinated and unvaccinated, the measurement of outcomes, and in the selection of participants.

Epidemiology

Complications Following SARS-CoV-2 Infection in Victoria, Australia: A Record Linkage Study
SARS-CoV-2 infection can induce significant pathologies including neurological, cardiac and vascular disease events. Researchers assessed strength of association between SARS-CoV-2 infection and several key respiratory and non-respiratory complications in Victoria, Australia. Record linkage was used to assemble all laboratory-confirmed COVID-19 cases notified 1 January 2020–31 May 2021 with corresponding hospitalization episodes to 30 September 2021. Hospitalization rates and reasons for hospitalization among cases was assessed using a cohort study design. A self-controlled case series was used to assess strength of association between SARS-CoV-2 infection and several outcomes in the first 90 days following COVID-19 illness onset. Incident rate ratios (IRR) and 95% confidence intervals were calculated comparing risk in the post-exposure period with a baseline period prior to SARS-CoV-2 infection. There were 20,594 COVID-19 cases, with 2,992 (14·53%) related hospitalizations. In the 90-days following COVID-19 illness onset, elevated risks were observed for myocarditis and pericarditis (IRR: 14·76, 95% confidence interval 3·19–68·30); thrombocytopenia (IRR: 7·38, 4·36–12·50), pulmonary embolism (IRR: 6·37; 3·55–11·43), acute myocardial infarction (IRR: 3·89, 2·59–5·84) and cerebral infarction and non-ischemic stroke (IRR: 2·31, 1·37–3·90). There is a strong association between SARS-CoV-2 infection and risk of several complications highlighting the value of COVID-19 pandemic mitigation measures such as vaccination. Improved awareness of these risks may support early diagnosis and management of patients with a past history of SARS-CoV-2 infection, and contribute to a greater understanding of the public health burden of COVID-19.
Risks of mental health outcomes in people with covid-19: cohort study
The objective of this study wasto estimate the risks of incident mental health disorders in survivors of the acute phase of covid-19. This was a cohort comprising 153 848 people who survived the first 30 days of SARS-CoV-2 infection, and two control groups: a contemporary group (n=5 637 840) with no evidence of SARS-CoV-2, and a historical control group (n=5 859 251) that predated the covid-19 pandemic. The covid-19 group showed an increased risk of incident anxiety disorders (hazard ratio 1.35 (95% confidence interval 1.30 to 1.39); risk difference 11.06 (95% confidence interval 9.64 to 12.53) per 1000 people at one year), depressive disorders (1.39 (1.34 to 1.43); 15.12 (13.38 to 16.91) per 1000 people at one year), stress and adjustment disorders (1.38 (1.34 to 1.43); 13.29 (11.71 to 14.92) per 1000 people at one year), and use of antidepressants (1.55 (1.50 to 1.60); 21.59 (19.63 to 23.60) per 1000 people at one year) and benzodiazepines (1.65 (1.58 to 1.72); 10.46 (9.37 to 11.61) per 1000 people at one year). The risk of any incident mental health diagnosis or prescription was increased (1.60 (1.55 to 1.66); 64.38 (58.90 to 70.01) per 1000 people at one year). The risks of examined outcomes were increased even among people who were not admitted to hospital and were highest among those who were admitted to hospital during the acute phase of covid-19. Results were consistent with those in the historical control group. The risk of incident mental health disorders was consistently higher in the covid-19 group in comparisons of people with covid-19 not admitted to hospital versus those not admitted to hospital for seasonal influenza, admitted to hospital with covid-19 versus admitted to hospital with seasonal influenza, and admitted to hospital with covid-19 versus admitted to hospital for any other cause. The findings suggest that people who survive the acute phase of covid-19 are at increased risk of an array of incident mental health disorders. Tackling mental health disorders among survivors of covid-19 should be a priority.
Association of Primary Care Physicians Per Capita With COVID-19 Vaccination Rates Among US Counties
Greater participation of primary care physicians (PCPs) in vaccine distribution has been proposed as a strategy to combat vaccine hesitancy. Therefore, researchers sought to examine the association of the number of PCPs per capita with COVID-19 vaccination rates among US counties. Researchers conducted a cross-sectional study of 2739 counties and county equivalents of the 3142 total counties in the US (87.2%) as of August 23, 2021. They linked the number of PCPs (including general family medicine, general practice, general internal medicine, and general pediatrics physicians) per 100 000 population for each county and other key variables with data on the percentage of the population who were fully vaccinated against SARS-CoV-2. They examined the associations between the number of PCPs per 100 000 population and COVID-19 vaccination rates by using generalized estimating equation models with robust SEs after accounting for clustering within states and county population weights. The multivariable models were adjusted for demographic factors, urbanicity, socioeconomic status, and political leaning. Among the 2739 US counties included in this study, PCPs were primarily concentrated in the Northeast, Florida, and many counties in the Midwest and West. This finding roughly corresponded to the distribution of counties with higher COVID-19 vaccination rates. After adjustment for potential confounders, counties in the highest decile of the number of PCPs per 100 000 population were associated with a 5.5% higher vaccination rate compared with those in the lowest decile (95% CI, 2.6%-8.4%). Every 10 additional PCPs per 100 000 population was associated with a 0.3% higher vaccination rate (95% CI, 0.2%-0.4%). In this cross-sectional study, researchers found that the number of PCPs per 100 000 population was independently associated with higher COVID-19 vaccination rates in the US. In conclusion, findings suggest that PCPs play a critical role in ensuring vaccine acceptance, especially in resource-limited and vaccine-hesitant regions, potentially through counseling and building local community trust and partnerships before they had access to vaccines.