Coronavirus COVID-19 Update for April 11, 2021

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Clinical Reports

Cardiac Complications After SARS-CoV-2 Infection and mRNA COVID-19 Vaccination — PCORnet, United States, January 2021–January 2022
Incidences of myocarditis and myocarditis or pericarditis were calculated after first, second, unspecified, or any (first, second, or unspecified) dose of mRNA COVID-19 (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) vaccines, stratified by sex and age group. Risk ratios (RR) were calculated to compare risk for cardiac outcomes after SARS-CoV-2 infection to that after mRNA COVID-19 vaccination. For every group, the risk for cardiac outcomes was significantly higher after infection. Even in the highest risk group, males aged 12–17 years after the second vaccine dose; the risk for cardiac outcomes was 8–5.6 times higher after SARS-CoV-2 infection than after the second vaccine dose. This can be reduced even more by delaying that second dose out to 8-12 weeks which would increase probably increase efficacy. It should be noted that cardiac issues post vaccine tend to be milder, shorter in duration and not the issues that have forced professional and collegiate athletes to drop out of competition.
Clinical characteristics, activity levels and mental health problems in children with long coronavirus disease: a survey of 510 children
They found in this cohort that participating children had had persistent COVID-19 for a mean of 8.2 months. Data was obtained on 510 children. 351 (68.8) of the children lived in the United Kingdom while 94 (18.4) lived in the United States. At their initial COVID-19 infection, only 22 (4.3%) children were hospitalized; 62 (12.2%) were asymptomatic, 378 (74.1%) were managed at home and 48 (9.4%) went to hospital but were not admitted. A total of 223 (43.7%) children had no pre-existing conditions, and the most frequent comorbidities were allergies (15.9%), asthma (14.5%), eczema (12.4%) and anxiety (7.1%). The most frequent symptoms were tiredness and weakness (87.1% of sample), fatigue (80.4% of sample), headache (78.6% of sample), stomach pain or cramps (75.9% of sample), muscle aches and pains (68.4% of sample), muscle and joint pain (60.6% of sample), postexertional malaise (53.7% of sample), rash (52.4% of sample), unexplained irritability (51.4% of sample) and dizziness (48% of sample). A total of 484 (94.9%) children had at least four symptoms. Researchers urged further research into long COVID, due to the lack of therapeutic options.
Short-term Outcomes of Corticosteroid Monotherapy in Multisystem Inflammatory Syndrome in Children
Researchers in this cohort study examined whether corticosteroid monotherapy is a viable treatment alternative for multisystem inflammatory syndrome. MIS-C is a syndrome where 3-4 weeks after an acute SARS-CoV-2 infection, a child develops an inflammatory syndrome with most cases having impacts on cardiac function, fever, and what appears to be a vasculitis with shock. To date this has been treated with steroids, IVIG, or both. These are the results from a retrospective cohort study that included 228 eligible patients and the analysis in is on 215 patients included in the analysis in a tertiary-care pediatric hospital system who had MIS-C per the Centers for Disease Control and Prevention case definition during the period March 2020 to February 2021. They compared treatment with corticosteroids alone to treatment with corticosteroids and IVIG. They performed propensity weight scoring because as one might imagine the group treated with corticosteroids as a group had milder disease. Propensity weight scoring is a method to try to improve the similarities between the two groups so we are not just comparing a group with milder disease to one with more severe disease. After propensity score weighting including 179 patients (68 in the corticosteroids group and 111 in the IVIG plus corticosteroids group), rates of initial treatment failure were similar between groups. The authors suggested it was reasonable to start with corticosteroid monotherapy based on this information as there are many disadvantages of including IVIG therapy as part of primary treatment including high cost (especially in low-income countries), potential shortages, interference with other serological diagnoses, and need to delay live viral vaccinations with a resultant risk of reemergence of vaccine-preventable diseases. In contrast corticosteroids are inexpensive and potentially effective in short courses.

Antiviral Therapeutics and Vaccines

Protection by a Fourth Dose of BNT162b2 against Omicron in Israel
Beginning early January, Israel became one of the first countries to administer a fourth dose of Pfizer’s BNT162b2 COVID19 vaccine to people 60 years or older. This was due to increased cases of COVID19 due to the Omicron variant. A study was conducted by the Israeli Ministry of Health to evaluate the effect of the fourth dose on confirmed cases of COVID19 as well as severe illness. The study showed that the number of severe COVID-19 per 100,000 person was 1.5 in the four-dose group, 3.9 in the three-dose group, and 4.2 in the internal control group. Long term data showed that rates of confirmed COVID19 infection and severe illness were lower after a fourth dose of Pfizer’s BNT162b2 vaccine. However, protection against infection was short term, with effectiveness waning after four weeks, and being nearly gone after eight weeks. Protection against severe illness did not wane during study period. Further studies are being conducted to evaluate long term effectiveness of protection against severe illness with a fourth dose.
Long-term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia
Researchers assessed 180-day mortality and health-related quality of life measures in a blinded trial where 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India were randomized to 6mg versus 12mg of dexamethasone. At 180 days, (33.7%) had died in the 12 mg group versus (38.6%) in the 6 mg group relative risk 0.89; 0.72–1.09;P = 0.13]. Dosage change did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose .
S. FDA has granted priority review to Roche’s Actemra (TOCILIZUMAB) for the treatment of COVID-19 in hospitalised adults
If approved, Actemra/RoActemra would be the first U.S. FDA-approved immunomodulator for the treatment of COVID-19 in hospitalized patients. The sBLA submission is based on results from four randomized, controlled studies that evaluated Actemra/RoActemra for the treatment of COVID-19 in more than 5,500 hospitalized patients. Altogether, the results of these four studies (EMPACTA, COVACTA, REMDACTA, and RECOVERY) suggest that Actemra/RoActemra may improve outcomes in patients receiving corticosteroids and requiring supplemental oxygen or breathing support. Since the beginning of the pandemic, more than one million people hospitalized with COVID-19 have been treated with Actemra/TOCILIZUMAB worldwide.

Epidemiology

The Concept of Classical Herd Immunity May Not Apply to COVID-19.
As commonly understood. herd immunity thresholds are reached when a sufficient proportion of the population is vaccinated or has recovered from natural infection with a pathogen such that its community circulation is reduced below the level of significant public health threat. For example, this threshold has been met with polio and measles circulation in the United States. However, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is so different from polio and measles that classical herd immunity may not readily apply to it. Important differences include the phenotypic stability of polio and measles viruses, and their ability to elicit long-term protective immunity, compared to SARS-CoV-2. For these and other reasons, controlling COVID-19 by increasing herd immunity may be an elusive goal.