March 23, 2023

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Clinical Reports

Prior COVID-19 infection associated with increased risk of newly diagnosed erectile dysfunction
- Researchers sought to assess if COVID-19 infection recovery is associated with increased rates of newly diagnosed erectile dysfunction. Using IBM MarketScan, a commercial claims database, men with prior COVID-19 infection were identified using ICD-10 diagnosis codes. Using this cohort along with an age-matched cohort of men without prior COVID-19 infection, researchers assessed the incidence of newly diagnosed erectile dysfunction. Covariates were assessed using a multivariable model to determine association of prior COVID-19 infection with newly diagnosed erectile dysfunction. 42,406 men experienced a COVID-19 infection between January 2020 and January 2021 of which 601 (1.42%) developed new onset erectile dysfunction within 6.5 months follow up. On multivariable analysis while controlling for diabetes, cardiovascular disease, smoking, obesity, hypogonadism, thromboembolism, and malignancy, prior COVID-19 infection was associated with increased risk of new onset erectile dysfunctio. Prior to the widespread implementation of the COVID-19 vaccine, the incidence of newly diagnosed erectile dysfunction is higher in men with prior COVID-19 infection compared to age-matched controls. Prior COVID-19 infection was associated with a 27% increased likelihood of developing new-onset erectile dysfunction when compared to those without prior infection.

Antiviral Therapeutics and Vaccines

A novel tool to eradicate an ancient scourge: the novel oral polio vaccine type 2 story
- The recent detection of vaccine-derived poliovirus (VDPV) in London (UK) and a case of paralytic polio in New York (USA) have highlighted how the scourge of poliomyelitis has not been totally overcome and remains an international problem, not confined to Afghanistan and Pakistan (where wild-type 1 poliovirus remains endemic) or as outbreaks of circulating VDPV in countries in Africa. To address the risk of circulating VDPVs, a global collaborative effort over the past decade has enabled the development of novel oral polio vaccine type 2 (nOPV2) that is as immunogenic as the current Sabin strain and so equally effective, while being less likely to revert to neurovirulence than Sabin oral polio vaccines. The successful development of nOPV2—the first such vaccine against type 2 poliovirus and the first vaccine ever authorised by the WHO Prequalification team through its Emergency Use Listing procedure—has led to the deployment of approximately 450 million doses of nOPV2 for outbreak control in 21 countries. It also paved the way for the subsequent Emergency Use Listing approval of COVID-19 vaccines in the global pandemic. Monitoring the use of nOPV2 has confirmed it is more genetically stable and less likely to result in VDPV than the Sabin strain, suggesting that the target of the global eradication of poliomyelitis might be a little more attainable than previously believed.
Correlates of protection against COVID-19 infection and intensity of symptomatic disease in vaccinated individuals exposed to SARS-CoV-2 in households
- Both IgG and neutralising antibodies are correlates of protection against SARS-CoV-2 infection. This data suggest that IgG concentrations higher than 500 BAU/mL and neutralising antibody titres of 1024 or more are thresholds for immunological protection from SARS-CoV-2 delta variant infection. Potentially, updated protective thresholds against emerging variants of concern could be calculated, which could support decision makers on administration of new vaccination strategies and on the optimal period between vaccine doses.
Effectiveness of nirmatrelvir–ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system
- 7274 nirmatrelvir–ritonavir recipients and 126 152 non-recipients with positive SARS-CoV-2 tests were included in our study. 5472 (75·2%) treatment recipients and 84 657 (67·1%) non-recipients were tested within 5 days of symptom onset. Nirmatrelvir–ritonavir had an overall estimated effectiveness of 53·6% (95% CI 6·6–77·0) in preventing hospital admission or death within 30 days of a positive test for SARS-CoV-2, which increased to 79·6% (33·9–93·8) when nirmatrelvir–ritonavir was dispensed within 5 days of symptom onset. Within the subgroup of patients tested within 5 days of symptom onset and whose treatment was dispensed on the day of their test, the estimated effectiveness of nirmatrelvir–ritonavir was 89·6% (50·2–97·8). In a setting with high levels of COVID-19 vaccine uptake, nirmatrelvir–ritonavir effectively reduced the risk of hospital admission or death within 30 days of a positive outpatient SARS-CoV-2 test.
Projected COVID-19 Mortality Reduction From Paxlovid Rollout
- Researchers estimated that 78% of US cases that will require hospitalization are detected within 5 days of symptom onset, and that uptake of Paxlovid is 5% among eligible infected individuals. Given Paxlovid effectiveness of 67% against hospitalization and 81% against mortality, this corresponds to relative percentage reductions of COVID-19 hospitalization by 2.7% and mortality by 3.2%. At 5% Paxlovid uptake, the required number of symptomatic tests and Paxlovid courses needed during the WOW would have been 4.8 million and 2.5 million, respectively, averting 2.7% of hospitalizations and 3.2% of deaths. At 80% Paxlovid uptake (model 8), the required number of symptomatic tests and Paxlovid courses would have been 75.3 million and 39.8 million, respectively, averting 41.8% of hospitalizations and 50.5% of deaths.
SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity
- mRNA-based vaccines dramatically reduce the occurrence and severity of COVID-19, but are associated with rare vaccine-related adverse effects. These toxicities, coupled with observations that SARS-CoV-2 infection is associated with autoantibody development, raise questions whether COVID-19 vaccines may also promote the development of autoantibodies, particularly in autoimmune patients. Here researchers used Rapid Extracellular Antigen Profiling to characterize self- and viral-directed humoral responses after SARS-CoV-2 mRNA vaccination in 145 healthy individuals, 38 patients with autoimmune diseases, and 8 patients with mRNA vaccine-associated myocarditis. Researchers confirm that most individuals generated robust virus-specific antibody responses post vaccination, but that the quality of this response is impaired in autoimmune patients on certain modes of immunosuppression. Autoantibody dynamics are remarkably stable in all vaccinated patients compared to COVID-19 patients that exhibit an increased prevalence of new autoantibody reactivities. Patients with vaccine-associated myocarditis do not have increased autoantibody reactivities relative to controls. In summary, these findings indicate that mRNA vaccines decouple SARS-CoV-2 immunity from autoantibody responses observed during acute COVID-19.

Epidemiology

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis
- Researchers screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias. This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

Correlates of protection and viral load trajectories in omicron breakthrough infections in triple vaccinated healthcare workers
- Vaccination offers protection against severe COVID-19 caused by SARS-CoV-2 omicron but is less effective against infection. Characteristics such as serum antibody titer correlation to protection, viral abundance and clearance of omicron infection in vaccinated individuals are scarce. Researcher present a 4-week twice-weekly SARS-CoV-2 qPCR screening in 368 triple vaccinated healthcare workers. Spike-specific IgG levels, neutralization titers and mucosal spike-specific IgA-levels were determined at study start and qPCR-positive participants were sampled repeatedly for two weeks. 81 (cumulative incidence 22%) BA.1, BA.1.1 and BA.2 infections were detected. High serum antibody titers are shown to be protective against infection (p < 0.01), linked to reduced viral load (p < 0.01) and time to viral clearance (p < 0.05). Pre-omicron SARS-CoV-2 infection is independently associated to increased protection against omicron, largely mediated by mucosal spike specific IgA responses (nested models lr test p = 0.02 and 0.008). Only 10% of infected participants remain asymptomatic through the course of their infection. We demonstrate that high levels of vaccine-induced spike-specific WT antibodies are linked to increased protection against infection and to reduced viral load if infected, and suggest that the additional protection offered by pre-omicron SARS-CoV-2 infection largely is mediated by mucosal spike-specific IgA.