Coronavirus COVID-19 Update for July 28, 2022

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Clinical Reports

Post–COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection
Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years and 994 (52.8%) were boys. A total of 110 SARS-CoV-2–positive children reported PCCs, including 44 of 447 hospitalized during the acute illness and 66 of 1437 children not hospitalized during the acute illness. Among SARS-CoV-2–positive children, the most common symptom was fatigue or weakness. Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization; having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms and being 14 years of age or older compared with younger than 1 year. SARS-CoV-2–positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized and those who were hospitalized. In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit, specifically systemic health problems (eg, fatigue, weakness, fever). In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.
Symptoms and risk factors for long COVID in non-hospitalized adults
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. Researchers undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. They selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02–8.39), hair loss (3.99, 3.63–4.39), sneezing (2.77, 1.40–5.50), ejaculation difficulty (2.63, 1.61–4.28) and reduced libido (2.36, 1.61–3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.

Antiviral Therapeutics and Vaccines

Safety and efficacy of molnupiravir in SARS-CoV-2 infected patients: a real-life experience
Researchers conducted a retrospective cohort study including all people treated with Molnupiravir between the 10th of January and the 31th of March 2022 at the University Hospital of Sassari. Molnupiravir was prescribed, according to the Italian Agency of Drug indications, in patients with recent symptoms onset (≤5five days), no need of oxygen supplementation, and with a high risk of disease progression for the presence chronic diseases. Study authors included 192 people with a mean age of 70.4±15.4 years; 144 (75%) patients were over 60 years. During the follow-up, 20 (10.4%) patients showed a disease progression. At the multivariate analysis, older age, having neurological disease, and having dyspnea at the onset of the symptoms, and acquiring SARS-CoV-2 infeciton during an hospital admission were associated with an increased risk of progression. On the contrary, early start of treatment was associated with a reduced risk of disease progression. Molnupiravir was also extremely safe since 13 (6.8%) adverse events were reported, with only one interruption. This study shows that Monlupiravir confirmed its efficacy and safety in a real-life cohort that included a high percentage of elderly people with a high comorbidity burden.
COVID-19 Vaccination Intent and Belief that Vaccination Will End the Pandemic
High vaccination coverage is considered to be key in dealing with the coronavirus disease (COVID-19) pandemic. However, vaccine hesitancy can limit uptake. Researchers examined the specific coronavirus beliefs that persons have regarding COVID-19 and COVID-19 vaccines and to what extent these beliefs explain COVID-19 vaccination intentions. Study authors conducted a survey among 4,033 residents of the Netherlands that examined COVID-19 vaccination intentions and various beliefs. Random forest regression analysis explained 76% of the variance in vaccination intentions. The strongest determinant in the model was the belief the COVID-19 crisis will only end if many persons get vaccinated. Other strong determinants were beliefs about safety of vaccines, specifically in relation to vaccine development and approval process; (social) benefits of vaccination; social norms regarding vaccination behavior; and effectiveness of vaccines. The study authors propose to address these specific beliefs in communications about COVID-19 vaccinations to stimulate vaccine uptake.
Antiviral drug treatment for nonsevere COVID-19: a systematic review and network meta-analysis
Molnupiravir and nirmatrelvir–ritonavir reduce risk of hospital admission and death among patients with nonsevere COVID-19. Compared with molnupiravir, nirmatrelvir–ritonavir reduces risk of hospital admission. Data from ongoing and future trials may improve the certainty of evidence and allow us to make stronger claims about the comparative efficacy of antiviral treatments.
Association of nirmatrelvir/ritonavir treatment on upper respiratory SARS-CoV-2 RT-PCR negative conversion rates among high-risk patients with COVID-19
There were 258 patients treated with nirmatrelvir/ritonavir and 224 non-treated patients who had mild-to-moderate COVID-19. The median (interquartile range) time for patients who converted from positive to negative RT-PCR was 10 days (7-12 days) in patients treated ≤5 days after symptom onset and 17 days (12-21 days) in non-treated patients, respectively. The proportions of patients with a negative conversion at day 15 were 89.7% and 42.0% in treated patients and non-treated patients, corresponding to a hazard ratio of 4.33 (95% CI, 3.31-5.65). Adjustment for baseline differences between the groups had little effect on the association. Subgroup analysis on treated patients suggests that time to negative conversion did not vary with the patients’ baseline characteristics. This cohort study of high-risk patients with mild-to-moderate COVID-19 found an association between nirmatrelvir/ritonavir treatment and accelerated negative RT-PCR respiratory SARS-CoV-2 conversion that might reduce the risk of viral shedding and disease transmission.
Enoxaparin for primary thromboprophylaxis in symptomatic outpatients with COVID-19 (OVID): a randomized, open-label, parallel-group, multicenter, phase 3 trial
Between Aug 15, 2020, and Jan 14, 2022, from 3319 participants prescreened, 472 were included in the intention-to-treat population and randomly assigned to receive enoxaparin (n=234) or standard of care (n=238). The median age was 57 years (IQR 53–62) and 217 (46%) were women. The 30-day risk of the primary outcome was similar in participants allocated to receive enoxaparin and in controls (8 [3%] of 234 vs8 [3%] of 238; adjusted relative risk 0·98; 95% CI 0·37–2·56; p=0·96). All hospitalizations were related to COVID-19. No deaths were reported during the study. No major bleeding events were recorded. Eight serious adverse events were recorded in the enoxaparin group versus nine in the control group. These findings suggest thromboprophylaxis with enoxaparin does not reduce early hospitalizations and deaths among outpatients with symptomatic COVID-19. Futility of the treatment under the initial study design assumptions could not be conclusively assessed owing to under-representation of older patients and consequent low event rates.
Statin and aspirin as adjuvant therapy in hospitalized patients with SARS-CoV-2 infection: a randomized clinical trial (RESIST trial)
In this single-center, open-label, randomized controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalization, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I. The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41–2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27–1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events. Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration.

Epidemiology

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.
Pregnancy outcomes after SARS-CoV-2 infection by trimester: A large, population-based cohort study
A total of 2753 /2789 (98.7%) eligible women that were infected during pregnancy could be matched, among them, 17.4% and 48.4% were infected during the first and third trimesters, respectively. While first and second trimester infections were not associated with PTB (p>0.8), third trimester infections and in particular after 34 weeks of gestation had a greater risk of PTB with adjusted ORs of 2.76 (95% CI 1.63–4.67) and 7.10 (95% CI 2.44–20.61), respectively. PTB risk was further heightened in symptomatic third trimester infections (OR = 4.28, 95% CI 1.94–9.25). SGA risk was comparable between study groups across all trimesters of infection. Pregnancy loss incidence was similar in both groups (adjusted OR = 1.16; 95% CI 0.90–1.50).
Smoking is associated with increased risk of cardiovascular events, disease severity, and mortality among patients hospitalized for SARS-CoV-2 infections
The clinical sequalae of SARS-CoV-2 infection are in part dependent upon age and pre-existing health conditions. Although the use of tobacco products decreases cardiorespiratory fitness while increasing susceptibility to microbial infections, limited information is available on how smoking affects COVID-19 severity. Therefore, researchers examined whether smokers hospitalized for COVID-19 are at a greater risk for developing severe complications than non-smokers. Data were from all hospitalized adults with SARS-CoV-2 infection from the American Heart Association’s Get-With-The-Guidelines COVID-19 Registry, from January 2020 to March 2021, which is a hospital-based voluntary national registry initiated in 2019 with 122 participating hospitals across the United States. Patients who reported smoking at the time of admission were classified as smokers. Severe outcome was defined as either death or the use of mechanical ventilation. Of the 31,545 patients in the cohort, 6,717 patients were 1:2 propensity matched (for age, sex, race, medical history, medications, and time-frame of hospital admission) and classified as current smokers or non-smokers according to admission data. In multivariable analyses, after adjusting for sociodemographic characteristics, medical history, medication use, and the time of hospital admission, patients self-identified as current smokers had higher adjusted odds of death (adjusted odds ratio [aOR], 1.41; 95% CI, 1.21–1.64), the use of mechanical ventilation (aOR 1.15; 95% CI 1.01–1.32), and increased risk of major adverse cardiovascular events (aOR, 1.27; 95% CI 1.05–1.52). Independent of sociodemographic characteristics and medical history, smoking was associated with a higher risk of severe COVID-19, including death.