February 2, 2023

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Clinical Reports

Information for Persons Who Are Immunocompromised Regarding Prevention and Treatment of SARS-CoV-2 Infection in the Context of Currently Circulating Omicron Sublineages — United States, January 2023
- COVID-19 vaccination remains the most effective way to prevent SARS-CoV-2–associated serious illness, hospitalization, and death. All persons, including those who are immunocompromised and their household members and close contacts, should stay up to date with COVID-19 vaccination, and receive the updated (bivalent) booster dose, when eligible. A recent CDC study of preliminary data showed that a bivalent booster dose provided additional protection against symptomatic SARS-CoV-2 infection among immunocompetent persons who had previously received 2, 3, or 4 monovalent vaccine doses. Among persons with immunocompromise and their household members and close contacts, prevention measures including wearing a high-quality and well-fitting mask, maintaining physical distance from others (≥6 ft [1.8 m]), improving indoor ventilation, practicing frequent handwashing, and developing a care plan, should be considered in addition to receipt of a bivalent booster dose. It is important to wear a mask and maintain physical distance from others if it is not possible to avoid crowded indoor spaces. In addition, simple interventions should be used to improve ventilation in buildings and decrease SARS-CoV-2 transmission by improving air flow. CDC has developed interactive tools¶¶ to help identify ways to improve ventilation in the home. In-duct ultraviolet germicidal irradiation lights can also be added to home heating ventilation and air conditioning systems to inactivate SARS-CoV-2 as air passes through the system. Frequent handwashing with soap and water is the best way to eliminate germs in most situations. If soap and water are not readily available, an alcohol-based hand sanitizer containing ≥60% alcohol is a good alternative. Also, it is important for persons who are immunocompromised to develop a care plan in consultation with their physician, in the event that they develop COVID-19. Persons with mild to moderate symptoms of COVID-19 who 1) are aged ≥50 years, 2) have an underlying health condition††† (especially moderate to severe immunosuppression), or 3) are unvaccinated are at risk for severe COVID-19–associated outcomes. Irrespective of vaccination status, symptomatic persons who are immunocompromised, their household members, and their close contacts should be tested for SARS-CoV-2 infection as soon as possible and receive treatment within 5–7 days of symptom onset. Early outpatient treatment of mild to moderate COVID-19 with a recommended first-line therapy, ritonavir-boosted nirmatrelvir (Paxlovid) or remdesivir (Veklury), or the second-line therapy, molnupiravir (Lagevrio), have been shown to reduce the risk for severe COVID-19, including hospitalization and death. These medications are expected to retain activity against the currently circulating Omicron sublineages and are widely available. Available COVID-19 treatment does not supplant the need for persons to stay up to date on their COVID-19 vaccinations, which are highly effective at preventing COVID-19–related morbidity and mortality.
Severe Fatigue and Persistent Symptoms at Three Months Following SARS-CoV-2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study
- This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, individual and organ system-based symptoms, and presence of ≥3 total symptoms across variants among COVID-positive and COVID-negative participants 3 months after their initial SARS-CoV-2 diagnosis. Variant periods were defined by dates with ≥50% dominant strain. Researchers performed a sensitivity analysis using ≥90% dominance threshold and multivariable logistic regression modeling to estimate the independent effects of each variant adjusting for socio-demographic characteristics, baseline health, and vaccine status. The study included 3,223 participants (2,402 COVID-positive and 821 COVID-negative). Among the COVID-positive cohort, 463 (19.3%) were pre-Delta, 1,198 (49.9%) during Delta, and 741 (30.8%) during Omicron. Prolonged severe fatigue was highest in the pre-Delta COVID-positive cohort compared with Delta and Omicron cohorts (16.7% vs 11.5% vs 12.3%, respectively; p = 0.017), as was presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; p < 0.001). No difference was seen in the COVID-negative cohort between variant time-periods. In multivariable models, there was no difference in severe fatigue between variants. There was decreased odds of having ≥3 symptoms in Omicron compared with other variants; this was not significant after adjusting for vaccination status. Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during the pre-Delta period compared with Delta and Omicron periods; however, these differences were no longer significant after adjusting for vaccination status. This suggests a potential beneficial effect of vaccination on the risk of developing long-term symptoms.

Antiviral Therapeutics and Vaccines

Reconsideration of Antinucleocapsid IgG Antibody as a Marker of SARS-CoV-2 Infection Postvaccination for Mild COVID-19 Patients
- Antinucleocapsid (anti-N) immunoglobulin G antibody responses were lower in plasma and oral fluid after severe acute respiratory syndrome coronavirus 2 infection in vaccinated patients compared with patients infected before vaccination or infected without vaccination. This raises questions about the long-term use of anti-N antibodies as a marker for natural infection for surveillance.

Effectiveness of Bivalent Boosters against Severe Omicron Infection
- Booster effectiveness peaked at approximately 4 weeks and waned afterward. For all participants 12 years of age or older, vaccine effectiveness against severe infection resulting in hospitalization over days 15 to 99 after receipt of one monovalent booster dose was 25.2% (95% confidence interval [CI], –0.2 to 44.2), and the corresponding vaccine effectiveness for one bivalent booster dose was 58.7% (95% CI, 43.7 to 69.8); the difference in vaccine effectiveness against this outcome between the bivalent booster and the monovalent booster was 33.5 percentage points (95% CI, 2.9 to 62.1). Vaccine effectiveness against severe infection resulting in hospitalization or death was 24.9% (95% CI, 1.4 to 42.8) for one monovalent booster dose and 61.8% (95% CI, 48.2 to 71.8) for one bivalent booster dose; the difference in vaccine effectiveness against this outcome between the bivalent booster and the monovalent booster was 36.9 percentage points (95% CI, 12.6 to 64.3). We obtained similar vaccine effectiveness estimates when the analysis was restricted to participants who were 18 years of age or older or 65 years of age or older, to participants who received an mRNA vaccine as their primary vaccine, or to previously uninfected participants. In addition, estimates of vaccine effectiveness were similar for the Moderna and Pfizer–BioNTech boosters and similar among the first, second, and third booster doses. Bivalent boosters provided substantial additional protection against severe omicron infection in persons who had previously been vaccinated or boosted, although the effectiveness waned over time. The effectiveness of bivalent boosters was higher than that of monovalent boosters.

Epidemiology

Prevalence and Clinical Outcomes of Respiratory Syncytial Virus versus Influenza in Adults Hospitalized with Acute Respiratory Illness from a Prospective Multicenter Study
- Current understanding of severe RSV infections in adults is limited by clinical under-recognition. Researchers compared the prevalence, clinical characteristics, and outcomes of RSV infections vs influenza in adults hospitalized with acute respiratory illnesses in a prospective national surveillance network. Hospitalized adults who met a standardized ARI case definition were prospectively enrolled across three respiratory seasons from hospitals participating across all sites of the U.S. Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN, 2016-2019). All participants were tested for RSV and influenza by RT-PCR. Multivariable logistic regression was used to test associations between laboratory-confirmed infection and characteristics and clinical outcomes. Among 10,311 hospitalized adults, 6% tested positive for RSV (n=622), 18.8% positive for influenza (n=1,940), and 75.1% negative for RSV and influenza (n=7,749). Congestive Heart Failure (CHF) or Chronic Obstructive Pulmonary Disease (COPD) was more frequent among adults with RSV than influenza (CHF: 37.3% vs. 28.8%, p<0.0001; COPD: 47.6% vs. 35.8%, p<0.0001). Patients with RSV more frequently had longer admissions [OR=1.38 (95% CI: 1.06-1.80) for stays >one week] and mechanical ventilation [OR=1.45 (95% CI: 1.09-1.93)] compared with influenza, but not compared to the influenza negative group [OR=1.03 (95% CI: 0.82-1.28); OR=1.17 (0.91-1.49), respectively.] The prevalence of RSV across three recent respiratory illness seasons was considerable. Our findings suggest those with RSV might incur worse outcomes than influenza in hospitalized adults and frequently have pre-existing cardiopulmonary conditions. This study informs future vaccination strategies and underscores a need for RSV surveillance among adults experiencing severe ARI.
Assessment of COVID-19 as the Underlying Cause of Death Among Children and Young People Aged 0 to 19 Years in the US
- There were 821 COVID-19 deaths among individuals aged 0 to 19 years during the study period, resulting in a crude death rate of 1.0 per 100 000 population overall; 4.3 per 100 000 for those younger than 1 year; 0.6 per 100 000 for those aged 1 to 4 years; 0.4 per 100 000 for those aged 5 to 9 years; 0.5 per 100 000 for those aged 10 to 14 years; and 1.8 per 100 000 for those aged 15 to 19 years. COVID-19 mortality in the time period of August 1, 2021, to July 31, 2022, was among the 10 leading causes of death in CYP aged 0 to 19 years in the US, ranking eighth among all causes of deaths, fifth in disease-related causes of deaths (excluding unintentional injuries, assault, and suicide), and first in deaths caused by infectious or respiratory diseases when compared with 2019. COVID-19 deaths constituted 2% of all causes of death in this age group. The findings of this study suggest that COVID-19 was a leading cause of death in CYP. It caused substantially more deaths in CYP annually than any vaccine-preventable disease historically in the recent period before vaccines became available. Various factors, including underreporting and not accounting for COVID-19’s role as a contributing cause of death from other diseases, mean that these estimates may understate the true mortality burden of COVID-19. The findings of this study underscore the public health relevance of COVID-19 to CYP. In the likely future context of sustained SARS-CoV-2 circulation, appropriate pharmaceutical and nonpharmaceutical interventions (eg, vaccines, ventilation, air cleaning) will continue to play an important role in limiting transmission of the virus and mitigating severe disease in CYP.
Association of culturable-virus detection and household transmission of SARS-CoV-2 – California and Tennessee, 2020–2022
- From two SARS-CoV-2 household transmission studies (enrolling April 2020 – January 2022) with rapid enrollment and specimen collection for 14 days, 61% (43/70) of primary cases had culturable-virus detected ≥6 days post-onset. Risk of secondary infection among household contacts tended to be greater when primary cases had culturable-virus detected after onset. Regardless of duration of culturable-virus, most secondary infections [70% (28/40)] had serial intervals <6 days, suggesting early transmission. These data examine viral culture as a proxy for infectiousness, reaffirm the need for rapid control measures after infection and highlight the potential for prolonged infectiousness (≥6 days) in many individuals.
Efficacy and safety of antimicrobial stewardship prospective audit and feedback in patients hospitalized with COVID-19 (COVASP): a pragmatic, cluster-randomized, non-inferiority trial
- Between March 1 and Oct 29, 2021, 1411 patients were screened and 886 were enrolled: 457 into the prospective audit and feedback plus standard of care group, of whom 429 completed the study, and 429 into the standard of care group, of whom 404 completed the study. Baseline characteristics were similar for both groups, with an overall mean age of 56·7 years (SD 17·3) and a median baseline ordinal scale of 4·0 (IQR 4·0–5·0). 301 audit and feedback events were recorded in the intervention group and 215 recommendations were made, of which 181 (84%) were accepted. Despite lower antibiotic use in the intervention group than in the control group (length of therapy 364·9 vs 384·2 days per 1000 patient days), clinical status at postadmission day 15 was non-inferior (median ordinal score 2·0 [IQR 2·0–3·0] vs 2·0 [IQR 2·0–4·0]; p=0·37, Mann-Whitney U test). Neutropenia was uncommon in both the intervention group (13 [3%] of 420 patients) and the control group (20 [5%] of 396 patients), and acute kidney injury occurred at a similar rate in both groups (74 [18%] of 421 patients in the intervention group and 76 [19%] of 399 patients in the control group). No intervention-related deaths were recorded. This cluster-randomized clinical trial shows that prospective audit and feedback is safe and effective in optimizing and reducing antibiotic use in adults admitted to hospital with COVID-19. Despite many competing priorities during the COVID-19 pandemic, antimicrobial stewardship should remain a priority to mitigate the overuse of antibiotics in this population.