September 29, 2022

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Clinical Reports

Increase in Acute Respiratory Illnesses Among Children and Adolescents Associated with Rhinoviruses and Enteroviruses, Including Enterovirus D68 — United States, July–September 2022
Enterovirus D68 (EV-D68) caused biennial outbreaks of severe respiratory illness and acute flaccid myelitis (AFM) in the United States in 2014, 2016, and 2018. After an extended period of low EV-D68 circulation during the COVID-19 pandemic, surveillance data suggest increased detection of rhinovirus/enterovirus and EV-D68, concurrent with increased emergency department visits by children and adolescents with acute respiratory illness and asthma/reactive airway disease during summer 2022. Clinicians should consider EV-D68 as a possible cause of acute respiratory illness and AFM in children and adolescents this fall and be aware of guidance for prompt testing and referral for patients with suspected AFM.
Monkeypox Virus Infection in Humans across 16 Countries — April–June 2022
Researchers report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having ≤10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported. In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.
Long Covid—An Update for Primary Care
Long Covid (prolonged symptoms following Covid-19 infection) is common. The mainstay of management is supportive, holistic care, symptom control, and detection of treatable complications. Many patients can be supported effectively in primary care by a GP with a special interest
A distinct symptom pattern emerges for COVID-19 long-haul: A Nationwide Study
Long-haul COVID-19, also called post-acute sequelae of SARS-CoV-2 (PASC), is a new illness caused by SARS-CoV-2 infection and characterized by the persistence of symptoms. The purpose of this cross-sectional study was to identify a distinct and significant temporal pattern of PASC symptoms (symptom type and onset) among a nationwide sample of PASC survivors (n = 5652). The sample was randomly sorted into two independent samples for exploratory (EFA) and confirmatory factor analyses (CFA). Five factors emerged from the EFA: (1) cold and flu-like symptoms, (2) change in smell and/or taste, (3) dyspnea and chest pain, (4) cognitive and visual problems, and (5) cardiac symptoms. The CFA had excellent model fit (x² = 513.721, df = 207, p < 0.01, TLI = 0.952, CFI = 0.964, RMSEA = 0.024). These findings demonstrate a novel symptom pattern for PASC. These findings can enable nurses in the identification of at-risk patients and facilitate early, systematic symptom management strategies for PASC.

Antiviral Therapeutics and Vaccines

SARS-CoV-2 Secondary Attack Rates in Vaccinated and Unvaccinated Household Contacts during Replacement of Delta with Omicron Variant, Spain
Researchers performed a prospective, cross-sectional study of household contacts of symptomatic index case-patients with SARS-CoV-2 infection during the shift from Delta- to Omicron-dominant variants in Spain. They included 466 household contacts from 227 index cases. The secondary attack rate was 58.2% (95% CI 49.1%–62.6%) during the Delta-dominant period and 80.9% (95% CI 75.0%–86.9%) during the Omicron-dominant period. During the Delta-dominant period, unvaccinated contacts had higher probability of infection than vaccinated contacts (odds ratio 5.42, 95% CI 1.6–18.6), but this effect disappeared at ≈20 weeks after vaccination. Contacts showed a higher relative risk of infection (9.16, 95% CI 3.4–25.0) in the Omicron-dominant than Delta-dominant period when vaccinated within the previous 20 weeks. Their data suggests vaccine evasion might be a cause of rapid spread of the Omicron variant. Researchers recommend a focus on developing vaccines with long-lasting protection against severe disease, rather than only against infectivity.
Breakthrough Infection by SARS-CoV-2 Delta and Omicron Variants Elicited Immune Response Comparable to mRNA Booster Vaccination
Both Delta and Omicron breakthrough infection elicited markedly high levels of serum total RBD Ig and neutralizing antibody, as well as T-cell responses in individuals who previously completed 2-dose vaccination. The levels of immune response were comparable to those receiving the heterologous mRNA booster vaccination.
Interval between prior SARS-CoV-2 infection and booster vaccination impacts magnitude and quality of antibody and B cell responses
SARS-CoV-2 mRNA booster vaccines provide protection from severe disease, eliciting strong immunity that is further boosted by previous infection. However, it is unclear whether these immune responses are affected by the interval between infection and vaccination. Over a two-month period, researchers evaluated antibody and B-cell responses to a third dose mRNA vaccine in 66 individuals with different infection histories. Uninfected and post-boost but not previously infected individuals mounted robust ancestral and variant spike-binding and neutralizing antibodies, and memory B cells. Spike-specific B-cell responses from recent infection (< 180 days) were elevated at pre-boost but comparatively less so at 60 days post-boost compared to uninfected individuals, and these differences were linked to baseline frequencies of CD27^loB cells. Day 60 to baseline ratio of BCR signaling measured by phosphorylation of Syk was inversely correlated to days between infection and vaccination. Thus, B-cell responses to booster vaccines are impeded by recent infection.
Further humoral immunity evasion of emerging SARS-CoV-2 BA.4 and BA.5 subvariants
Researchers findings suggest that significant humoral immune evasion, especially against convalescents from BA.4 and BA.5 breakthrough infection, contributes to the emergence and rapid spread of multiple Arg346-mutated BA.4 and BA.5 sublineages. The decreased neutralization titres of plasma samples from BA.5 breakthrough-infection convalescents indicate worrisome potential reinfection of BA.4.6 after the recovery from BA.4 or BA.5 infection. Importantly, individuals that received Evusheld as long-term prophylaxis, especially those that are immunodeficient or exhibit high-risk comorbidities, are at particular risk of those subvariants. Also, BA.4 and BA.5-based vaccine boosting strategies should be evaluated in light of the prevalence of these BA.4 and BA.5 subvariants.
Short-course Early Outpatient Remdesivir Prevents Severe Disease due to COVID-19 in Organ Transplant Recipients During the Omicron BA.2 Wave
Solid organ transplant recipients (SOTr) remain at risk of severe COVID-19. Several previous early therapies are no longer effective against new circulating variants. Researchers performed a prospective cohort study in outpatient adult SOTr during the Omicron BA.2 wave (April-May 2022), to determine the effectiveness of 3 doses of remdesivir given within 7 days of symptoms onset. Patients were followed for at least 30 days. The primary outcome was hospitalization. Of 210 SOTr that had COVID-19, we included 192. The median age was 54.5 years and 61.5% were men. The most common transplants were kidney (41.7%), lung (19.3%), liver (18.8%), and heart (6.3%). Most patients (90.1%) had previously received ≥3 COVID-19 vaccine doses. Fifteen(7.8%) were hospitalized, 5(2.6%) required supplemental oxygen, 3(1.6%) ICU admission, and 2(1%) mechanical ventilation with 2(1%) deaths. Age and multiple comorbidities were risk factors for hospitalization. Early remdesivir significantly decreased the hospitalization rate: adjusted hazard ratio 0.12 (95%CI: 0.03 to 0.057). The adjusted number needed to treat to prevent one hospitalization was 15.2 (95%CI: 13.6 to 31.4). No patient that received early remdesivir needed ICU admission or died. In a cohort of SOTr with COVID-19 infection, administration of 3-dose early remdesivir independently reduced the disease severity.
Effectiveness of Molnupiravir in High Risk Patients: a Propensity Score Matched Analysis
Molnupiravir was granted emergency use authorization for the treatment of mild to moderate COVID-19. In this study researchers used population-based real-world data to evaluate the effectiveness of Molnupiravir. The database of the largest healthcare provider in Israel was used to identify all adults with first ever positive test for SARS-CoV-2 performed in the community during January-February 2022, who were at high risk for severe COVID-19 and had no contraindications for Molnupiravir use. Patients were included regardless of SARS-CoV-2 vaccination status. A total of 2661 patients who received Molnupiravir were propensity score-matched with 2661 patients who have not received Molnupiravir (control group). Patients were followed through 10 March 2022 for up to 28 days for the first occurrence of the composite severe COVID-19 or COVID-19 specific mortality. The composite outcome occurred in 50 patients in the Molnupiravir group and 60 patients in the control group. Molnupiravir was associated with a nonsignificant reduced risk of the composite outcome HR, 0.83 (95% CI, 0.57-1.21). However, subgroup analyses showed that Molnupiravir was associated with a significant decrease in the risk of the composite outcome in older patients 0.54 (0.34-0.86), in females 0.41 (0.22-0.77), and in patients with inadequate COVID-19 vaccination 0.45 (0.25-0.82). The results were similar when each component of the composite outcome were examined separately. This study suggests that in the era of omicron and in real life setting Molnupiravir might be effective in reducing the risk of severe COVID-19 and COVID-19 related mortality, particularly in specific subgroups.

Epidemiology

Early Estimates of Monkeypox Incubation Period, Generation Time, and Reproduction Number, Italy, May–June 2022
Researchers analyzed the first 255 PCR-confirmed cases of monkeypox in Italy in 2022. Preliminary estimates indicate mean incubation period of 9.1 (95% CI 6.5–10.9) days, mean generation time of 12.5 (95% CI 7.5–17.3) days, and reproduction number among men who have sex with men of 2.43 (95% CI 1.82–3.26).
Rapid Increase in Suspected SARS-CoV-2 Reinfections, Clark County, Nevada, USA, December 2021
Genetic differences between SARS-CoV-2 variants raise concerns about reinfection. Public health authorities monitored the incidence of suspected reinfection in Clark County, Nevada, USA, during March 2020–March 2022. Suspected reinfections, defined as a second positive PCR test collected >90 days after an initial positive test, were monitored through an electronic disease surveillance system. Researchers calculated the proportion of all new cases per week that were suspected reinfections and rates per 1,000 previously infected persons by demographic groups. The rate of suspected reinfection remained <7% until December 2021, then increased to ≈11%, corresponding with local Omicron variant detection. Reinfection rates were higher among adults 18–50 years of age, women, and minority groups, especially persons identifying as American Indian/Alaska Native. Suspected reinfection became more common in Clark County after introduction of the Omicron variant, and some demographic groups are disproportionately affected. Public health surveillance could clarify the SARS-CoV-2 reinfection burden in communities.