October 13, 2022

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Clinical Reports

A healthcare-associated infection with Monkeypox virus of a healthcare worker during the 2022 outbreak
This article describes a case of healthcare-associated Monkeypox infection in France during the 2022 outbreak. A female medical resident accidently pricked herself with a soiled subcutaneous needle used to harvest a patient infected by Monkeypox virus and developed 4 days later a unique skin lesion, positive for Monkeypox virus.

Antiviral Therapeutics and Vaccines

Tolerability and immunogenicity of an intranasally-administered adenovirus-vectored COVID-19 vaccine: An open-label partially-randomized ascending dose phase I trial
Researchers performed a single-centre open-label Phase I clinical trial of intranasal vaccination with ChAdOx1 nCoV-19 in healthy adults, using the existing formulation produced for intramuscular administration. Thirty SARS-CoV-2 vaccine-naïve participants were allocated to receive 5 × 10⁹viral particles (VP, n=6), 2 × 10¹⁰ VP (n=12), or 5 × 10¹⁰ VP (n=12). Fourteen received second intranasal doses 28 days later. A further 12 received non-study intramuscular mRNA SARS-CoV-2 vaccination between study days 22 and 46. To investigate intranasal ChAdOx1 nCoV-19 as a booster, six participants who had previously received two intramuscular doses of ChAdOx1 nCoV-19 and six who had received two intramuscular doses of BNT162b2 (Pfizer / BioNTech) were given a single intranasal dose of 5 × 10¹⁰ VP of ChAdOx1 nCoV-19. Reactogenicity was mild or moderate. Antigen-specific mucosal antibody responses to intranasal vaccination were detectable in a minority of participants, rarely exceeding levels seen after SARS-CoV-2 infection. Systemic responses to intranasal vaccination were typically weaker than after intramuscular vaccination with ChAdOx1 nCoV-19. Antigen-specific mucosal antibody was detectable in participants who received an intramuscular mRNA vaccine after intranasal vaccination. Seven participants developed symptomatic SARS-CoV-2 infection. This formulation of intranasal ChAdOx1 nCoV-19 showed an acceptable tolerability profile but induced neither a consistent mucosal antibody response nor a strong systemic response.
Clinical, Virologic, and Immunologic Evaluation of Symptomatic Coronavirus Disease 2019 Rebound Following Nirmatrelvir/Ritonavir Treatment
Six individuals with relapse of COVID-19 symptoms after treatment with nirmatrelvir/ritonavir, 2 individuals with rebound symptoms without prior antiviral therapy and 7 patients with acute Omicron infection (controls) were studied. Soluble biomarkers and serum SARS-CoV-2 nucleocapsid protein were measured. Nasal swabs positive for SARS-CoV-2 underwent viral isolation and targeted viral sequencing. SARS-CoV-2 anti-spike, anti–receptor-binding domain, and anti-nucleocapsid antibodies were measured. Surrogate viral neutralization tests against wild-type and Omicron spike protein, as well as T-cell stimulation assays, were performed. High levels of SARS-CoV-2 anti-spike immunoglobulin G (IgG) antibodies were found in all participants. Anti-nucleocapsid IgG and Omicron-specific neutralizing antibodies increased in patients with rebound. Robust SARS-CoV-2–specific T-cell responses were observed, higher in rebound compared with early acute COVID-19 patients. Inflammatory markers mostly decreased during rebound. Two patients sampled longitudinally demonstrated an increase in activated cytokine-producing CD4⁺T cells against viral proteins. No characteristic resistance mutations were identified. SARS-CoV-2 was isolated by culture from 1 of 8 rebound patients; Polybrene addition increased this to 5 of 8. Nirmatrelvir/ritonavir treatment does not impede adaptive immune responses to SARS-CoV-2. Clinical rebound corresponds to development of a robust antibody and T-cell immune response, arguing against a high risk of disease progression. The presence of infectious virus supports the need for isolation and assessment of longer treatment courses.
Early outpatient treatment with remdesivir in patients at high risk for severe COVID-19: a prospective cohort study
From December 1^st, 2021, to April 30^th, 2022, a total of 196 high-risk patients were diagnosed with COVID-19, of which 126 were included in this study (43%, 54/126 received remdesivir, 57%, 72/126 did not receive remdesivir). Baseline clinical characteristics were similar between groups; autoimmune diseases (39/126), solid organ transplant (31/126) and malignant neoplasms (24/126) were the most common immunocompromising conditions. Diabetes mellitus was strongly associated with the primary outcome in both groups. Prior SARS-CoV-2 infection or vaccination were not independently associated with COVID-19 progression. Treatment with remdesivir significantly reduced the odds of hospitalization or death (adjusted HR 0.16 95% CI 0.06 to 0.44, p < 0.01). Early outpatient treatment with remdesivir significantly reduces hospitalization or death by 84% in high-risk, majority immunosuppressed patients with COVID-19 Omicron variant.
Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): preliminary analysis from the United Kingdom randomized, controlled open-label, platform adaptive trial
Between December 8, 2021 and April 27, 2022, 25783 participants were randomized to molnupiravir plus usual care (n=12821) or usual care alone (n=12962). Mean (range) age of participants was 56·6 years (18 to 99), 58·6% were female, and 99% had at least one dose of a SARS-CoV-2 vaccine. The median duration of symptoms prior to randomization was two days (IQR 1 – 3), the median number of days from symptom onset to starting to take the medication was three days (IQR 3 – 4), 87% (11109/11997) received their medication within five days of symptom onset, and 95·4% (n=11857) of participants randomized to molnupiravir reported taking molnupiravir for five days. Primary outcome measure data were available in 25000 (97%) participants and included in this analysis. 103/12516 (0·8%) hospitalizations/deaths occurred in the molnupiravir group versus 96/12484 (0·8%) in usual care alone with a posterior probability of superiority of 0·34 (adjusted odds ratio 1·061 (95% Bayesian credible interval [BCI]) 0·80 to 1·40). Estimates were similar for all subgroups. The observed median (IQR) time-to-first-recovery from randomization was 9 (5–23) days in molnupiravir and 15 (7–not reached) days in usual care. There was an estimated benefit of 4·2 (95% BCI: 3·8 – 4·6) days in time-to-first-recovery (TTR) giving a posterior probability of superiority of >0·999 (estimated median TTR 10·3 [10·2 – 10·6] days vs 14·5 [14·2 – 14·9] days respectively; hazard ratio [95% BCI], 1·36 [1·3–1·4] days), which met the pre-specified superiority threshold. On day 7, SARS-CoV-2 virus was below detection levels in 7/34 (21%) of the molnupiravir group, versus 1/39 (3%) in the usual care group (p=0.039), and mean viral load was lower in the molnupiravir group compared with those receiving usual care [(SD) of log10(viral load) 3·82 (1·40) in the molnupiravir group and 4.93 (1·38) in the usual care group, (P<0·001)]. 59 (0·4%) participants experienced serious adverse events in the molnupiravir group and 52 (0·4%) in usual care. In this preliminary analysis, we found that molnupiravir did not reduce already low hospitalizations/deaths among higher risk, vaccinated adults with COVID-19 in the community, but resulted in faster time to recovery, and reduced viral detection and load.

Epidemiology

Air and surface sampling for monkeypox virus in a UK hospital
Researchers identified widespread surface contamination (56 [93%] of 60 samples were positive) in occupied patient rooms (monkeypox DNA cycle threshold [Ct] values 24·7–37·4), on health-care worker PPE after use (Ct 26·1–35·6), and in PPE doffing areas (Ct 26·3–36·8). Of 20 air samples taken, five (25%) were positive. Three (75%) of four air samples collected before and during a bedding change in one patient's room were positive (Ct 32·7–36·2). Replication-competent virus was identified in two (50%) of four samples selected for viral isolation, including from air samples collected during bedding change. This data shows contamination in isolation facilities and potential for suspension of monkeypox virus into the air during specific activities. PPE contamination was observed after clinical contact and changing of bedding. Contamination of hard surfaces in doffing areas supports the importance of cleaning protocols, PPE use, and doffing procedures.

Misrepresentation and Nonadherence Regarding COVID-19 Public Health Measures
This survey assessed 9 different types of misrepresentation and nonadherence related to COVID-19 public health measures and the reasons underlying such behaviors. Additional questions measured COVID-19–related beliefs and behaviors and demographic characteristics. The final sample included 1733 participants. The mean (SD) participant age was 41 (15) years and the sample predominantly identified as female (1143 of 1732 [66.0%]) and non-Hispanic White (1151 of 1733 [66.4%]). Seven hundred twenty-one participants (41.6%) reported misrepresentation and/or nonadherence in at least 1 of the 9 items; telling someone they were with or about to be with in person that they were taking more COVID-19 preventive measures than they actually were (420 of 1726 [24.3%]) and breaking quarantine rules (190 of 845 [22.5%]) were the most common manifestations. The most commonly endorsed reasons included wanting life to feel normal and wanting to exercise personal freedom. All age groups younger than 60 years (eg, odds ratio for those aged 18-29 years, 4.87 [95% CI, 3.27-7.34]) and those who had greater distrust in science (odds ratio, 1.14 [95% CI, 1.05-1.23]) had significantly higher odds of misrepresentation and/or nonadherence for at least 1 of the 9 items. In this survey study of US adults, nearly half of participants reported misrepresentation and/or nonadherence regarding public health measures against COVID-19. Future work is needed to examine strategies for communicating the consequences of misrepresentation and nonadherence and to address contributing factors.
Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study
With increasing numbers infected by SARS-CoV-2, understanding long-COVID is essential to inform health and social care support. A Scottish population cohort of 33,281 laboratory-confirmed SARS-CoV-2 infections and 62,957 never-infected individuals were followed-up via 6, 12 and 18-month questionnaires and linkage to hospitalization and death records. Of the 31,486 symptomatic infections,1,856 (6%) had not recovered and 13,350 (42%) only partially. No recovery was associated with hospitalized infection, age, female sex, deprivation, respiratory disease, depression and multimorbidity. Previous symptomatic infection was associated with poorer quality of life, impairment across all daily activities and 24 persistent symptoms including breathlessness (OR 3.43, 95% CI 3.29–3.58), palpitations (OR 2.51, OR 2.36–2.66), chest pain (OR 2.09, 95% CI 1.96–2.23), and confusion (OR 2.92, 95% CI 2.78–3.07). Asymptomatic infection was not associated with adverse outcomes. Vaccination was associated with reduced risk of seven symptoms.