November 09, 2022

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Clinical Reports

Low Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Transmission by Fomites: A Clinical Observational Study in Highly Infectious Coronavirus Disease 2019
The contribution of droplet-contaminated surfaces for virus transmission has been discussed controversially in the context of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. More importantly, the risk of fomite-based transmission has not been systematically addressed. Therefore, the aim of this study was to evaluate whether confirmed hospitalized coronavirus disease 2019 (COVID-19) patients can contaminate stainless steel carriers by coughing or intensive moistening with saliva and to assess the risk of SARS-CoV-2 transmission upon detection of viral loads and infectious virus in cell culture. Researchers initiated a single-center observational study including 15 COVID-19 patients with a high baseline viral load (cycle threshold value ≤25). Researchers documented clinical and laboratory parameters and used patient samples to perform virus culture, quantitative polymerase chain reaction, and virus sequencing. Nasopharyngeal and oropharyngeal swabs of all patients were positive for viral ribonucleic acid on the day of the study. Infectious SARS-CoV-2 could be isolated from 6 patient swabs (46.2%). After coughing, no infectious virus could be recovered, however, intensive moistening with saliva resulted in successful viral recovery from steel carriers of 5 patients (38.5%). Transmission of infectious SARS-CoV-2 via fomites is possible upon extensive moistening, but it is unlikely to occur in real-life scenarios and from droplet-contaminated fomites.
Nucleocapsid Antigenemia Is a Marker of Acute SARS-CoV-2 Infection
Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is essential for diagnosis, treatment, and infection control. Polymerase chain reaction (PCR) fails to distinguish acute from resolved infections, as RNA is frequently detected after infectiousness. Researchers hypothesized that nucleocapsid in blood marks acute infection with the potential to enhance isolation and treatment strategies. In a retrospective serosurvey of inpatient and outpatient encounters, researchers categorized samples along an infection timeline using timing of SARS-CoV-2 testing and symptomatology. Among 1860 specimens from 1607 patients, the highest levels and frequency of antigenemia were observed in samples from acute SARS-CoV-2 infection. Antigenemia was higher in seronegative individuals and in those with severe disease. In their analysis, antigenemia exhibited 85.8% sensitivity and 98.6% specificity as a biomarker for acute coronavirus disease 2019 (COVID-19). Thus, antigenemia sensitively and specifically marks acute SARS-CoV-2 infection. Further study is warranted to determine whether antigenemia may aid individualized assessment of active COVID-19.
Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution
Continuous evolution of Omicron has led to numerous subvariants that exhibit growth advantage over BA.5. Such rapid and simultaneous emergence of variants with enormous advantages is unprecedented. Despite their rapidly divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots, including R346, K356, K444, L452, N460K and F486. The driving force and destination of such convergent evolution and its impact on humoral immunity established by vaccination and infection remain unclear. Here, researchers demonstrate that these convergent mutations can cause striking evasion of convalescent plasma, including those from BA.5 breakthrough infection, and existing antibody drugs, including Evusheld and Bebtelovimab. BR.2, CA.1, BQ.1.1, BM.1.1.1, and especially XBB, are the most antibody-evasive strain tested, far exceeding BA.5 and approaching SARS-CoV-1 level. To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies (mAbs) isolated from BA.2 and BA.5 breakthrough-infection convalescents. Importantly, due to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection caused significant reductions in the epitope diversity of neutralizing antibodies and increased proportion of non-neutralizing mAbs, which in turn concentrated humoral immune pressure and promoted the convergent RBD evolution. Additionally, the precise convergent RBD mutations and evolution trends of BA.2.75/BA.5 subvariants could be inferred by integrating the neutralization-weighted DMS profiles of mAbs from various immune histories (3051 mAbs in total). Moreover, we demonstrated that as few as five additional convergent mutations based on BA.5 or BA.2.75 could completely evade most plasma samples, including those from BA.5 breakthrough infection, while retaining sufficient hACE2-binding affinity. These results suggest that current herd immunity and BA.5 vaccine boosters may not provide sufficiently broad protection against infection. Broad-spectrum SARS-CoV-2 vaccines and NAb drugs development should be of high priority, and the constructed convergent mutants could serve to examine their effectiveness in advance.
Can SARS-CoV-2 trigger new onset of autoimmune disease in adults? A case-based review
SARS-CoV-2 can trigger new onset of a variety of autoimmune diseases. Doctors who take care patients infected by COVID-19 must be aware of the complications of autoimmune diseases. Future cohort or cross-sectional studies on SARS-CoV-2-related autoimmune disease should be conducted.

Antiviral Therapeutics and Vaccines

Protection against Omicron from Vaccination and Previous Infection in a Prison System
Information regarding the protection conferred by vaccination and previous infection against infection with the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is limited. Researchers evaluated the protection conferred by mRNA vaccines and previous infection against infection with the omicron variant in two high-risk populations: residents and staff in the California state prison system. Study authors used a retrospective cohort design to analyze the risk of infection during the omicron wave using data collected from December 24, 2021, through April 14, 2022. Weighted Cox models were used to compare the effectiveness (measured as 1 minus the hazard ratio) of vaccination and previous infection across combinations of vaccination history (stratified according to the number of mRNA doses received) and infection history (none or infection before or during the period of B.1.617.2 [delta]–variant predominance). A secondary analysis used a rolling matched-cohort design to evaluate the effectiveness of three vaccine doses as compared with two doses. Among 59,794 residents and 16,572 staff, the estimated effectiveness of previous infection against omicron infection among unvaccinated persons who had been infected before or during the period of delta predominance ranged from 16.3% (95% confidence interval [CI], 8.1 to 23.7) to 48.9% (95% CI, 41.6 to 55.3). Depending on previous infection status, the estimated effectiveness of vaccination (relative to being unvaccinated and without previous documented infection) ranged from 18.6% (95% CI, 7.7 to 28.1) to 83.2% (95% CI, 77.7 to 87.4) with two vaccine doses and from 40.9% (95% CI, 31.9 to 48.7) to 87.9% (95% CI, 76.0 to 93.9) with three vaccine doses. Incremental effectiveness estimates of a third (booster) dose (relative to two doses) ranged from 25.0% (95% CI, 16.6 to 32.5) to 57.9% (95% CI, 48.4 to 65.7) among persons who either had not had previous documented infection or had been infected before the period of delta predominance. Study findings in two high-risk populations suggest that mRNA vaccination and previous infection were effective against omicron infection, with lower estimates among those infected before the period of delta predominance. Three vaccine doses offered significantly more protection than two doses, including among previously infected persons.
Nirmatrelvir and the Risk of Post-Acute Sequelae of COVID-19
Long Covid – the disease encompassing the post-acute sequelae of SARS-CoV-2 (PASC) —affects millions of people around the world. Prevention of PASC is an urgent public health priority. In this work, researchers aimed to examine whether treatment with nirmatrelvir in the acute phase of COVID-19 is associated with reduced risk of post-acute sequelae. Researchers used the healthcare databases of the US Department of Veterans Affairs to identify users of the health system who had a SARS-CoV-2 positive test between March 01, 2022 and June 30, 2022, were not hospitalized on the day of the positive test, had at least 1 risk factor for progression to severe COVID-19 illness and survived the first 30 days after SARS-CoV-2 diagnosis. Researchers identified those who were treated with oral nirmatrelvir within 5 days after the positive test (n=9217) and those who received no COVID-19 antiviral or antibody treatment during the acute phase of SARS-CoV-2 infection (control group, n= 47,123). Inverse probability weighted survival models were used to estimate the effect of nirmatrelvir (versus control) on a prespecified panel of 12 post-acute COVID-19 outcomes and reported as hazard ratio (HR) and absolute risk reduction (ARR) in percentage at 90 days. Compared to the control group, treatment with nirmatrelvir was associated with reduced risk of PASC (HR 0.74 95% CI (0.69, 0.81), ARR 2.32 (1.73, 2.91)) including reduced risk of 10 of 12 post-acute sequelae in the cardiovascular system (dysrhythmia and ischemic heart disease), coagulation and hematologic disorders (deep vein thrombosis, and pulmonary embolism), fatigue, liver disease, acute kidney disease, muscle pain, neurocognitive impairment, and shortness of breath. Nirmatrelvir was also associated with reduced risk of post-acute death (HR 0.52 (0.35, 0.77), ARR 0.28 (0.14, 0.41)), and post-acute hospitalization (HR 0.70 (0.61, 0.80), ARR 1.09 (0.72, 1.46)). Nirmatrelvir was associated with reduced risk of PASC in people who were unvaccinated, vaccinated, and boosted, and in people with primary SARS-CoV-2 infection and reinfection. In sum, results show that in people with SARS-CoV-2 infection who had at least 1 risk factor for progression to severe COVID-19 illness, treatment with nirmatrelvir within 5 days of a positive SARS-CoV-2 test was associated with reduced risk of PASC regardless of vaccination status and history of prior infection. The totality of findings suggests that treatment with nirmatrelvir during the acute phase of COVID-19 reduces the risk of post-acute adverse health outcomes.
Bebtelovimab for high-risk outpatients with early COVID-19 in a large US health system
There are limited data for the clinical efficacy of bebtelovimab in preventing severe COVID-19. Among outpatients unable to take nirmatrelvir-ritonavir at a large health system, 10 of 377 (2.7%) patients who received bebtelovimab and 17 of 377 (4.5%) matched untreated patients were hospitalized or died. The 43% observed risk reduction with bebtelovimab was not statistically significant (p = 0.14).
Retrospectively modeling the effects of increased global vaccine sharing on the COVID-19 pandemic
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused considerable morbidity and mortality worldwide. The protection provided by vaccines and booster doses offered a method of mitigating severe clinical outcomes and mortality. However, by the end of 2021, the global distribution of vaccines was highly heterogeneous, with some countries gaining over 90% coverage in adults, whereas others reached less than 2%. In this study, researchers used an age-structured model of SARS-CoV-2 dynamics, matched to national data from 152 countries in 2021, to investigate the global impact of different potential vaccine sharing protocols that attempted to address this inequity. Researchers quantified the effects of implemented vaccine rollout strategies on the spread of SARS-CoV-2, the subsequent global burden of disease and the emergence of novel variants. Study authors found that greater vaccine sharing would have lowered the total global burden of disease, and any associated increases in infections in previously vaccine-rich countries could have been mitigated by reduced relaxation of non-pharmaceutical interventions. These results reinforce the health message, pertinent to future pandemics, that vaccine distribution proportional to wealth, rather than to need, may be detrimental to all.

Epidemiology

Epidemiologic and Clinical Features of Children and Adolescents Aged <18 Years with Monkeypox — United States, May 17–September 24, 2022
During May 17–September 24, 2022, Monkeypox virus(MPXV) infections in children and adolescents aged <18 years were rare, representing 0.3% of all U.S. cases; none resulted in critical illness or death. Younger children typically acquired MPXV infection after skin-to-skin contact with a household member with monkeypox during caregiving activities; adolescents were most frequently exposed through male-to-male sexual contact. Additional monkeypox cases in children and adolescents might be prevented through strengthened vaccination efforts and education around preventive measures and sexual health.
Impact of community masking on COVID-19: A cluster-randomized trial in Bangladesh
Mask usage remains low across many parts of the world during the COVID-19 pandemic, and strategies to increase mask-wearing remain untested. Researcher’s objectives were to identify strategies that can persistently increase mask-wearing and assess the impact of increasing mask-wearing on symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Researchers conducted a cluster-randomized trial of community-level mask promotion in rural Bangladesh from November 2020 to April 2021 (N= 600 villages, N = 342,183 adults). They cross-randomized mask promotion strategies at the village and household level, including cloth versus surgical masks. All intervention arms received free masks, information on the importance of masking, role modeling by community leaders, and in-person reminders for 8 weeks. The control group did not receive any interventions. Participants and surveillance staff were not informed of treatment assignments, but project materials were clearly visible. Outcomes included symptomatic SARS-CoV-2 seroprevalence (primary) and prevalence of proper mask-wearing, physical distancing, social distancing, and symptoms consistent with COVID-19 illness (secondary). Mask-wearing and distancing were assessed through direct observation at least weekly at mosques, markets, the main entrance roads to villages, and tea stalls. Individuals were coded as physically distanced if they were at least one arm’s length from the nearest adult; social distancing was measured using the total number of adults observed in public areas. At 5- and 9-week follow-ups, researchers surveyed all reachable participants about COVID-19–related symptoms. Blood samples collected at 10- to 12-week follow-ups for symptomatic individuals were analyzed for SARS-CoV-2 immunoglobulin G (IgG) antibodies. There were 178,322 individuals in the intervention group and 163,861 individuals in the control group. The intervention increased proper mask-wearing from 13.3% in control villages (N = 806,547 observations) to 42.3% in treatment villages (N = 797,715 observations) (adjusted percentage point difference = 0.29; 95% confidence interval = [0.26, 0.31]). This tripling of mask usage was sustained during the intervention period and for 2 weeks after. Physical distancing increased from 24.1% in control villages to 29.2% in treatment villages (adjusted percentage point difference = 0.05 [0.04, 0.06]). Researchers saw no change in social distancing. After 5 months, the impact of the intervention on mask-wearing waned, but mask-wearing remained 10 percentage points higher in the intervention group. Beyond the core intervention of free distribution and promotion at households, mosques, and markets; leader endorsements; and periodic monitoring and reminders, several elements had no additional effect on mask-wearing, including text reminders, public signage commitments, monetary or nonmonetary incentives, and altruistic messaging or verbal commitments. The proportion of individuals with COVID-19–like symptoms was 7.63% (N = 12,784) in the intervention arm and 8.60% (N = 13,287) in the control arm, an estimated 11.6% reduction after controlling for baseline covariates. Blood samples were collected from consenting, symptomatic adults (N = 10,790). Adjusting for baseline covariates, the intervention reduced symptomatic seroprevalence by 9.5% (adjusted prevalence ratio = 0.91 [0.82, 1.00]; control prevalence = 0.76%; treatment prevalence = 0.68%). Researchers find that surgical masks are particularly effective in reducing symptomatic seroprevalence of SARS-CoV-2. In villages randomized to surgical masks (N = 200), the relative reduction was 11.1% overall (adjusted prevalence ratio = 0.89 [0.78, 1.00]). The effect of the intervention is most concentrated among the elderly population; in surgical mask villages, researchers observe a 35.3% reduction in symptomatic seroprevalence among individuals ≥60 years old (adjusted prevalence ratio = 0.65 [0.45, 0.85]). They saw larger reductions in symptoms and symptomatic seropositivity in villages that experienced larger increases in mask use. No adverse events were reported. A randomized-trial of community-level mask promotion in rural Bangladesh during the COVID-19 pandemic shows that the intervention increased mask usage and reduced symptomatic SARS-CoV-2 infections, demonstrating that promoting community mask-wearing can improve public health.