Coronavirus COVID-19 Update for May 5, 2022

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Clinical Reports

Unravelling the Treatment Effect of Baricitinib on Clinical Progression and Resource Utilization in Hospitalized COVID-19 Patients: Secondary Analysis of the Adaptive COVID-19 Treatment Randomized Trial-2
In this study, the authors characterized the clinical trajectories of 891 ACTT-2 participants requiring supplemental oxygen or higher levels of respiratory support at enrollment. They estimated the effect of baricitinib on cumulative incidence of clinical improvement and deterioration using competing risks models. They developed multistate models (MSM) to estimate the effect of BCT on clinical improvement and deterioration, and on utilization of respiratory therapies. They found that Baricitinib resulted in more improvement and lower incidence of clinical deterioration compared with Remdesivir monotherapy (HR, 0.74; 95% CI, 0.58–0.95). Baricitinib did not benefit participants who were mechanically ventilated at enrollment.

Cortical Grey Matter Volume Loss links to Neurological Sequelae in post COVID-19 “Long Haulers”
This study involved 19 consecutive post COVID-19 surviving “long haulers” who experienced neurologic symptoms. Each patient had Brain MRI with 3-dimensional voxel-based morphometry (3D VBM) at median time of 72 days following laboratory confirmation. All patients had relatively mild respiratory symptoms which did not require oxygen supplementation, hospitalization, or assisted ventilation. 3-dimensional voxel-based morphometry (3D VBM) was obtained for whole brain, forebrain parenchyma, cortical grey matter, hippocampus, and thalamus. Researchers found that there was a statistically significant loss of cortical grey matter (CGM) volume in each COVID-19 “long hauler”.

Impact of Timing of Tocilizumab Use in Hospitalized Patients With SARS-CoV-2 Infection
This was a retrospective chart review of 11,512 patients infected with SARS-CoV-2 who were admitted to a New York health system from March to May 2020. The NY Health System was Northwell. The overall hospital mortality was significantly reduced in the tocilizumab group when tocilizumab was administered at the nasal cannula level (10.4% vs 22.0%; P = .002). In subjects who received tocilizumab at the nasal cannula level, the progression to mechanical ventilation was reduced versus subjects who were initially on higher levels of oxygen support (6.3% vs 18.7%; P < .001). There was no improvement in mortality when tocilizumab was given at the time of requiring non-rebreather, high-flow nasal cannula, noninvasive ventilator, or invasive ventilator.

Children and COVID-19: State Date 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: 4/28/22. 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

Comparative effectiveness over time of the mRNA-1273 (Moderna) vaccine and the BNT162b2 (Pfizer-BioNTech) vaccine
These are the results of a retrospective cohort study using deidentified administrative claims for 3.5 million fully vaccinated individuals in a research database, with a follow-up period between 14 and 151 days after their second dose. The primary outcome was the rate of Covid-19 infection occurring at 30, 60, and 90 days at least 14 days after the second dose of either the mRNA-1273 vaccine or the BNT162b2 vaccine. Sub-analyses included the incidence of hospitalization, ICU admission, and death/hospice transfer. Separate analysis was conducted for individuals above and below age 65 and those without a prior diagnosis of Covid-19. In this cohort immunization with mRNA-1273 (Moderna), compared to BNT162b2 )the Pfizer-BioNTech vaccine), provided slightly more protection against SARS-CoV-2 infection that reached statistical significance at 90 days with a number needed to vaccinate of> There are no differences in vaccine effectiveness for protection against hospitalization, ICU admission, or death/hospice transfer (aOR 1.23, 95% CI (0.67, 2.25)).

Pfizer Shares Top-Line Results from Phase 2/3 EPIC-PEP Study of PAXLOVID™ for Post-Exposure Prophylactic Use
This trial involved 2,957 adults. Enrolled adults had a negative SARS-CoV-2 rapid antigen test result and were asymptomatic household contacts with exposure within 96 hours to an individual who was symptomatic and recently tested positive for SARS-CoV-2. Each patient was randomized (1:1:1) to receive orally twice daily one of the following: (i) PAXLOVID for five days followed by placebo for 5 days, (ii) PAXLOVID for ten days or (iii) placebo for ten days. In this trial, compared to placebo, Pfizer observed risk reductions of 32% and 37% in adults who received PAXLOVID for five and ten days, respectively, to prevent infection. These results were not statistically significant and, as such, the primary endpoint of reducing the risk of confirmed and symptomatic COVID-19 infection in adults who had been exposed to the virus through a household contact was not met.

Rapid Relapse of Symptomatic SARS-CoV-2 Infection Following Early Suppression with Nirmatrelvir/Ritonavir
Initiation of NM/R treatment on Day 0 in a 71-year-old vaccinated and boosted male resulted in rapid resolution of COVID-19 symptoms followed one week later by the development of typical cold symptoms. SARS-CoV-2 viral load fluctuated in parallel with symptoms, with two distinct peaks on Day 1 and Day 9 of illness. No other respiratory pathogens were identified. Viral samples demonstrated sequence identity for the omicron subvariant BA.1 on Days 1, 7, and 11. These findings suggest that viral replication and COVID-19 symptoms may recur after very early treatment with NM/R before natural immunity is sufficient to fully clear SARS-CoV-2.

FDA Updates on Paxlovid for Health Care Providers
In this CDER Conversation, Dr. John Farley, director of the Office of Infectious Diseases, provides useful information that can help health care providers in decision making regarding Paxlovid, the preferred therapy for the management of non-hospitalized adults with COVID-19. Paxlovid is now widely available in community pharmacies. Although the number of COVID-19 hospitalizations has decreased dramatically since early 2022, some high-risk patients are still getting sick enough to require hospital admission, and early treatment with Paxlovid and other available authorized or approved therapeutics could make a difference.

Updated Information on Availability and Use of Treatments for Outpatients with Mild to Moderate COVID-19 Who are at Increased Risk for Severe Outcomes of COVID-19
The Centers for Disease Control and Prevention (CDC) has issued this Health Alert Network (HAN) Health Advisory to update healthcare providers, public health departments, and the public about the availability and use of recommended therapies for COVID-19 and to advise against using unproven treatments that have known or potential harms for outpatients with mild to moderate COVID-19. For patients with mild to moderate COVID-19 who are not hospitalized and who are at increased risk for severe COVID-19 outcomes, several treatment options, including antiviral medications and monoclonal antibodies, are now widely available and accessible. Systemic corticosteroids are not recommended to treat patients with mild to moderate COVID-19 who do not require supplemental oxygen; patients who are receiving dexamethasone or another corticosteroid for other indications should continue therapy for their underlying conditions as directed by their healthcare providers. Antibacterial therapy is not recommended for the treatment of COVID-19 in the absence of another indication. Staying up to date with COVID-19 vaccination is still the best way to prevent serious outcomes of COVID19, including severe disease, hospitalization, and death.

Pre-Hospital Administration of Remdesivir During a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Outbreak in a Skilled Nursing Facility
Study authors reported on the experience at the Idaho State Veteran’s Home-Boise (ISVH-B), a state-owned, 124-bed skilled nursing facility. Beginning on 31 October 2020, all patients with a SARS-CoV-2 diagnosis within the preceding 10 days were offered a 5-day course of remdesivir. They reported that completion of a 5-day course of remdesivir was associated with approximately 17-fold increased odds of survival among a sample of 54 nursing home residents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the course of an outbreak from October to December 2020.

Remdesivir and three other drugs for hospitalized patients with COVID-19: final results of the WHO Solidarity randomized trial and updated meta-analyses
Between March 22, 2020, and Jan 29, 2021, 14, 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14,221 patients, including 8,275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82–1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89–1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76–0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46–1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76–0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77–1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75–0·93], p=0·001). Allocation to daily remdesivir infusions (vsopen-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomized trials of remdesivir versus no remdesivir yielded similar findings. Remdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalized patients, it has a small effect against death or progression to ventilation (or both).

Diagnostics

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: January 2022 update on the use of therapeutic-intensity anticoagulation in acutely ill patients.
These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians and other health care professionals in decisions about the use of anticoagulation in patients with COVID-19. This is an update to guidelines published in February 2021 as part of the living phase of these guidelines. The panel made one additional recommendation. The panel issued a conditional recommendation in favor of therapeutic-intensity over prophylactic-intensity anticoagulation in patients with COVID-19-related acute illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of thrombotic and bleeding risk. The panel also noted that heparin (unfractionated or low-molecular-weight) may be preferred because of a preponderance of evidence with this class of anticoagulants. This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation in patients with COVID-19-related acute illness.

Epidemiology

SARS-CoV-2 Omicron Variant is as Deadly as Previous Waves After Adjusting for Vaccinations, Demographics, and Comorbidities
Study investigators linked state-level vaccination data with quality-controlled electronic health records from a large healthcare system, including 13 hospitals, in Massachusetts, USA. They then performed a weighted case-control study to compare risks of hospital admission and mortality across the SARS-CoV-2 waves in over 130,000 COVID patients. They found that after adjusting for confounders including various demographics, Charlson comorbidity index scores, and vaccination status (and holding the healthcare utilization constant), that the risks of hospitalization and mortality were nearly identical between periods. Their analysis suggested that the intrinsic severity of the Omicron variant may be as severe as previous variants.

Interleukin-6 inhibitors reduce mortality in coronavirus disease-2019: An individual patient data meta-analysis from randomized controlled trials
Eleven studies were identified, incorporating 7467 patients (IL-6 inhibitors: 4103, SOC: 3364). IL-6 inhibitors were associated with decreased risk for death compared to SOC at the one-stage meta-analysis (Hazard Ratio [HR]: 0.75, 95% Confidence interval [CI]: 0.69–0.82, p<0.0001) and the two-stage meta-analysis (HR: 0.85, 95%CI: 0.77–0.93, p<0.001, I²= 0.0%). Meta-regression analysis revealed that the difference in OS between the two groups was not influenced by the mean age of patients. At secondary meta-analyses, IL-6 inhibitors were associated with decreased odds for intubation OR:0.74, 95%CI:0.65–0.85, p<0.001, I2=0.0%). IL-6 inhibitors were associated with increased odds for discharge compared to SOC (OR:1.28, 95% CI:1.15–1.42, p<0.001, I2=0.0%).