Coronavirus COVID-19 Update for April 11, 2021

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Clinical Reports

Management of hair loss after severe acute respiratory syndrome coronavirus 2 infection: Insight into the pathophysiology with implication for better management
Numerous studies have reported impaired health sequelae after COVID-19 recovery, one of which is hair loss. Individuals with hair loss experience a substantial mental burden, which potentially hinders their social life. However, few studies have systematically analyzed the details including hair loss. Therefore, researchers conducted a narrative review using PubMed on the frequency, associated comorbidities, disease characteristics, and treatment of hair loss after SARS-CoV-2 infection (HLASCI). Two search strings were used to identify 28 articles. Of note, most of the literature identified on COVID-19 sequelae reported a emergence/occurrence of hair loss. HLASCI is speculated to be composed of a heterogeneous population, with the onset or exacerbation of telogen effluvium (TE), anagen effluvium, androgenetic alopecia (AGA), and alopecia areata (AA) reported as possible underlying mechanisms. Among these, acute TE is thought to be the primary cause of HLASCI, with COVID-19 treatment and TE improvement being considered crucial for HLASCI management. An association between COVID-19 and AA exacerbation has also been implicated with still insufficient evidence. Spontaneous recovery of TE can be expected once infection reduces; however, faster improvement in symptoms is expected to reduce the mental and social burden of patients. An additional search string identified 11 articles about TE treatment which suggested that the use of minoxidil may be beneficial. Topical minoxidil has been widely used for AGA patients, who have been speculated to exhibit poor resistance to SARS-CoV-2. Topical minoxidil may provide relief from HLASCI, but future clinical research is warranted to confirm this observation.
Children and COVID-19: State level Data Report
A joint report from the American Academy of Pediatrics and the Children’s Hospital Association. Summary of publicly reported data from 49 states, NYC, DC, PR, and GU Version: 6/02/22. The numbers in this report represent cumulative counts since states began reporting. The data are based on how public agencies collect, categorize and post information. All data reported by state/local health departments are preliminary and subject to change and reporting may change over time. Notably, in the summer of 2021 and winter of 2022, some states have revised cases counts previously reported, begun reporting less frequently, or dropped metrics previously reported. For example, due to several changes on their dashboards and the data currently available, AL, TX, HI, DC and MS data in this report are not current (cumulative data through 7/29/21, 8/26/21, 1/13/22, 3/3/22, and 3/10/22 respectively). Readers should consider these factors. States may have additional information on their web sites.

Antiviral Therapeutics and Vaccines

FDA Announces Tentative Advisory Committee Meeting Schedule Regarding COVID- 19 Vaccines
On May 23, the FDA revised the dates of the upcoming Vaccines and Related Biological Products Advisory Committee meetings due to new data from sponsors and expected submissions of emergency use authorization (EUA) requests. The new dates are as follows: June 14 will be the new meeting date for the FDA and its advisory committee of external experts to discuss Moderna’s EUA request for 6 years through 17 years of age. June 15 will be the new meeting date for the Moderna EUA request for 6 months through 5 years of age and Pfizer-BioNTech EUA request for 6 months through 4 years of age, based on expected completion of an EUA submission.
FDA Advisory Committee Recommends Emergency Use Authorization of Novavax COVID-19 Vaccine for People Aged 18 Years and Older
The FDA’s Vaccines and Related Biological Products Advisory Committee voted “yes” in response to a question of “Do the benefits of Novavax’s vaccine, given as a two-dose primary series, outweigh its risks in people 18 and older, based on available evidence.” Twenty-one members voted yes, one abstained, and none voted no.
Moderna announces omicron-containing bivalent booster candidate MRNA-1273.214 demonstrates superior antibody response against Omicron
Moderna, Inc., (NASDAQ:MRNA) a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced new clinical data on its Omicron-containing bivalent COVID booster candidate, mRNA-1273.214, containing mRNA-1273 (Spikevax) and a vaccine candidate targeting the Omicron variant of concern. A 50 µg booster dose of mRNA-1273.214 met all pre-specified endpoints including superior neutralizing antibody response (geometric mean ratio) against the Omicron variant one month after administration when compared to the original mRNA-1273 vaccine. The booster dose of mRNA-1273.214 was generally well-tolerated, with side effects comparable to a booster dose of mRNA-1273 at the 50 µg dose level. mRNA-1273.214 met all primary endpoints in the Phase 2/3 trial including neutralizing antibody response against Omicron when compared to a 50 µg booster dose of mRNA-1273 in baseline seronegative participants. Pre-specified criteria for superiority as measured by neutralizing geometric mean titer ratio (GMR) with the lower bound of the confidence interval >1 was met. The GMR and corresponding 97.5% confidence interval was 1.75 (1.49, 2.04). A booster dose of mRNA-1273.214 increased neutralizing geometric mean titers (GMT) against Omicron approximately 8-fold above baseline levels. Primary endpoints of non-inferiority against ancestral SARS-CoV-2 were also met, with GMR against ancestral SAR-COV-2 (D614G) of 1.22 (1.08-1.37).
Association of COVID-19 Vaccination During Pregnancy With Incidence of SARS-CoV-2 Infection in Infants
The objective of this study was to determine whether COVID-19 vaccination in pregnancy was associated with reduced risk of COVID-19 in infants up to age 4 months during COVID-19 pandemic periods dominated by Delta and Omicron variants. This nationwide, register-based cohort study included all live-born infants born in Norway between September 1, 2021, and February 28, 2022. Maternal messenger RNA COVID-19 vaccination during second or third trimester compared with no vaccination before or during pregnancy. The risk of a positive polymerase chain reaction test result for SARS-CoV-2 during an infant’s first 4 months of life by maternal vaccination status during pregnancy with either dose 2 or 3 was estimated, as stratified by periods dominated by the Delta variant (between September 1 and December 31, 2021) or Omicron variant (after January 1, 2022, to the end of follow-up on April 4, 2022). A Cox proportional hazard regression was used, adjusting for maternal age, parity, education, maternal country of birth, and county of residence. Of 21 643 live-born infants, 9739 (45.0%) were born to women who received a second or third dose of a COVID-19 vaccine during pregnancy. The first 4 months of life incidence rate of a positive test for SARS-CoV-2 was 5.8 per 10 000 follow-up days. Infants of mothers vaccinated during pregnancy had a lower risk of a positive test compared with infants of unvaccinated mothers and lower risk during the Delta variant–dominated period (incidence rate, 1.2 vs 3.0 per 10 000 follow-up days; adjusted hazard ratio, 0.29; 95% CI, 0.19-0.46) compared with the Omicron period (incidence rate, 7.0 vs 10.9 per 10 000 follow-up days; adjusted hazard ratio, 0.67; 95% CI, 0.57-0.79). The results of this Norwegian population-based cohort study suggested a lower risk of a positive test for SARS-CoV-2 during the first 4 months of life among infants born to mothers who were vaccinated during pregnancy. Maternal COVID-19 vaccination may provide passive protection to young infants, for whom COVID-19 vaccines are currently not available.
Population-level implications of the Israeli booster campaign to curtail COVID-19 resurgence
Israel was one of the first countries to administer mass vaccination against severe acute respiratory syndrome coronavirus 2. Consequently, it was among the first countries to experience substantial breakthrough infections due to the waning of vaccine-induced immunity, which led to a resurgence of the epidemic. In response, Israel launched a booster campaign to mitigate the outbreak and was the first country to do so. Israel’s success in curtailing the Delta resurgence while imposing only mild nonpharmaceutical interventions influenced the decision of many countries to initiate a booster campaign. By constructing a detailed mathematical model and calibrating it to the Israeli data, researchers extend the understanding of the impact of the booster campaign from the individual to the population level. Researchers used the calibrated model to explore counterfactual scenarios in which the booster vaccination campaign is altered by changing the eligibility criteria or the start time of the campaign and to assess the direct and indirect effects in the different scenarios. The results point to the vast benefits of vaccinating younger age groups that are not at a high risk of developing severe disease but play an important role in transmission. It is show further that, when the epidemic is exponentially growing, the success of the booster campaign is highly sensitive to the timing of its initiation. Hence, a rapid response is an important factor in reducing disease burden using booster vaccination.
Oral Nirmatrelvir and Severe Covid-19 Outcomes During the Omicron Surge
Nirmatrelvir, an inhibitor of the main protease of severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), has demonstrated a significant decrease in the risk of progression to severe disease in symptomatic high-risk patients infected with the B.1.617.2 (delta) variant of SARS-CoV-2. The effectiveness of nirmatrelvir against the B.1.1.529 variant (omicron) is unknown. The study included all Clalit Health Services members, 40 years of age and older, with confirmed infection of SARS-CoV-2 during the omicron surge that were defined as high-risk for severe disease. A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association between nirmatrelvir treatment and hospitalizations and deaths due to Covid-19, with adjustment for individual sociodemographic factors, coexisting conditions, and prior Covid-19 immunity status. 109,213 participants were eligible for nirmatrelvir therapy during the two-month study period. Among the 42,819 eligible patients aged 65 years and above, 2,504 were treated with nirmatrelvir. Hospitalizations due to Covid-19 occurred in 14 out of the treated and 762 of the untreated patients: adjusted HR 0.33 (95% CI, 0.19 to 0.55). Death due to Covid-19 occurred in 2 treated and 151 untreated patients; adjusted HR: 0.19 (95% CI, 0.05 to 0.76). Among the 66,394 eligible patients 40 to 64 years of age, 1,435 were treated with nirmatrelvir. Hospitalizations due to Covid-19 occurred in 9 treated and 334 untreated patients: adjusted HR 0.78 (95% CI, 0.40 to 1.53). Death due to Covid-19 occurred in 1 treated and 13 untreated patients; adjusted HR: 1.64 (95% CI, 0.40 to 12.95). Nirmatrelvir therapy was associated with a 67% reduction in Covid-19 hospitalizations and an 81% reduction in Covid-19 mortality in patients 65 years and above. However, no significant benefit in avoidance of severe Covid-19 outcomes was shown in younger adults.
Efficacy and safety of intramuscular administration of tixagevimab–cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial
Early intramuscular administration of SARS-CoV-2-neutralising monoclonal antibody combination, tixagevimab–cilgavimab, to non-hospitalized adults with mild to moderate COVID-19 has potential to prevent disease progression. Researchers aimed to evaluate the safety and efficacy of tixagevimab–cilgavimab in preventing progression to severe COVID-19 or death. TACKLE is an ongoing, phase 3, randomized, double-blind, placebo-controlled study conducted at 95 sites in the USA, Latin America, Europe, and Japan. Eligible participants were non-hospitalized adults aged 18 years or older with a laboratory-confirmed SARS-CoV-2 infection (determined by RT-PCR or an antigen test) from any respiratory tract specimen collected 3 days or less before enrolment and who had not received a COVID-19 vaccination. A WHO Clinical Progression Scale score from more than 1 to less than 4 was required for inclusion and participants had to receive the study drug 7 days or less from self-reported onset of mild to moderate COVID-19 symptoms or measured fever. Participants were randomly assigned (1:1) to receive either a single tixagevimab–cilgavimab 600 mg dose (two consecutive 3 mL intramuscular injections, one each of 300 mg tixagevimab and 300 mg cilgavimab) or placebo. Randomization was stratified (using central blocked randomization with randomly varying block sizes) by time from symptom onset, and high-risk versus low-risk of progression to severe COVID-19. Participants, investigators, and sponsor staff involved in the treatment or clinical evaluation and monitoring of the participants were masked to treatment-group assignments. The primary endpoints were severe COVID-19 or death from any cause through to day 29, and safety. Between Jan 28, 2021, and July 22, 2021, 1014 participants were enrolled, of whom 910 were randomly assigned to a treatment group (456 to receive tixagevimab–cilgavimab and 454 to receive placebo). The mean age of participants was 46·1 years (SD 15·2). Severe COVID-19 or death occurred in 18 (4%) of 407 participants in the tixagevimab–cilgavimab group versus 37 (9%) of 415 participants in the placebo group (relative risk reduction 50·5% [95% CI 14·6–71·3]; p=0·0096). The absolute risk reduction was 4·5% (95% CI 1·1–8·0; p<0·0001). Adverse events occurred in 132 (29%) of 452 participants in the tixagevimab–cilgavimab group and 163 (36%) of 451 participants in the placebo group, and were mostly of mild or moderate severity. There were three COVID-19-reported deaths in the tixagevimab–cilgavimab group and six in the placebo group. A single intramuscular tixagevimab–cilgavimab dose provided statistically and clinically significant protection against progression to severe COVID-19 or death versus placebo in unvaccinated individuals and safety was favorable. Treating mild to moderate COVID-19 earlier in the disease course with tixagevimab–cilgavimab might lead to more favorable outcomes.

Diagnostics

Diagnostic accuracy of non-invasive detection of SARS-CoV-2 infection by canine olfaction
Throughout the COVID-19 pandemic, testing individuals remains a key action. One approach to rapid testing is to consider the olfactory capacities of trained detection dogs. Prospective cohort study in two community COVID-19 screening centers. Two nasopharyngeal swabs (NPS), one saliva and one sweat samples were simultaneously collected. The dog handlers (and the dogs…) were blinded with regards to the Covid status. The diagnostic accuracy of non-invasive detection of SARS-CoV-2 infection by canine olfaction was assessed as compared to nasopharyngeal RT-PCR as the reference standard, saliva RT-PCR and nasopharyngeal antigen testing. 335 ambulatory adults (143 symptomatic and 192 asymptomatic) were included. Overall, 109/335 participants tested positive on nasopharyngeal RT-PCR either in symptomatic (78/143) or in asymptomatic participants (31/192). The overall sensitivity of canine detection was 97% (95% CI, 92 to 99) and even reached 100% (95% CI, 89 to 100) in asymptomatic individuals compared to NPS RT-PCR. The specificity was 91% (95% CI, 72 to 91), reaching 94% (95% CI, 90 to 97) for asymptomatic individuals. The sensitivity of canine detection was higher than that of nasopharyngeal antigen testing (97% CI: 91 to 99 versus 84% CI: 74 to 90, p = 0.006), but the specificity was lower (90% CI: 84 to 95 versus 97% CI: 93 to 99, p = 0.016). Non-invasive detection of SARS-CoV-2 infection by canine olfaction could be one alternative to NPS RT-PCR when it is necessary to obtain a result very quickly according to the same indications as antigenic tests in the context of mass screening.

Epidemiology

Efficacy of short-course colchicine treatment in hospitalized patients with moderate to severe COVID-19 pneumonia and hyperinflammation: a randomized clinical trial
Some patients with COVID-19 pneumonia develop an associated cytokine storm syndrome that aggravates the pulmonary disease. These patients may benefit of anti-inflammatory treatment. The role of colchicine in hospitalized patients with COVID-19 pneumonia and established hyperinflammation remains unexplored. In a prospective, randomized controlled, observer-blinded endpoint, investigator-initiated trial, 240 hospitalized patients with COVID-19 pneumonia and established hyperinflammation were randomly allocated to receive oral colchicine or not. The primary efficacy outcome measure was a composite of non-invasive mechanical ventilation (CPAP or BiPAP), admission to the intensive care unit, invasive mechanical ventilation requirement or death. The composite primary outcome occurred in 19.3% of the total study population. The composite primary outcome was similar in the two arms (17% in colchicine group vs. 20.8% in the control group; p = 0.533) and the same applied to each of its individual components. Most patients received steroids (98%) and heparin (99%), with similar doses in both groups. In this trial, including adult patients with COVID-19 pneumonia and associated hyperinflammation, no clinical benefit was observed with short-course colchicine treatment beyond standard care regarding the combined outcome
Factors Associated With Readmission in the United States Following Hospitalization With Coronavirus Disease 2019
In this analysis, researchers estimated the rate and risk factors associated with COVID-19–related readmission and inpatient mortality. In this retrospective cohort study, we used deidentified chargemaster data from 297 hospitals across 40 US states on patients hospitalized with COVID-19 from 15 February 2020 through 9 June 2020. Demographics, comorbidities, acute conditions, and clinical characteristics of first hospitalization are summarized. Multivariable logistic regression was used to measure risk factor associations with 30-day readmission and in-hospital mortality. Among 29 659 patients, 1070 (3.6%) were readmitted. Readmitted patients were more likely to have diabetes, hypertension, cardiovascular disease (CVD), or chronic kidney disease (CKD) vs those not readmitted (P < .0001) and to present on first admission with acute kidney injury (15.6% vs 9.2%), congestive heart failure (6.4% vs 2.4%), or cardiomyopathy (2.1% vs 0.8%) (P < .0001). Higher odds of readmission were observed in patients aged >60 vs 18–40 years (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.48–2.50) and those admitted in the Northeast vs West (OR, 1.43; 95% CI, 1.14–1.79) or South (OR, 1.28; 95% CI, 1.11–1.49). Comorbidities including diabetes (OR, 1.34; 95% CI, 1.12–1.60), CVD (OR, 1.46; 95% CI, 1.23–1.72), CKD stage 1–5 (OR, 1.51; 95% CI, 1.25–1.81), and CKD stage 5 (OR, 2.27; 95% CI, 1.81–2.86) were associated with higher odds of readmission; 12.3% of readmitted patients died during second hospitalization. Among this large US population of patients hospitalized with COVID-19, readmission was associated with certain comorbidities and acute conditions during first hospitalization. These findings may inform strategies to mitigate risks of readmission due to COVID-19 complications.