Short-Term Instantaneous Prophylaxis and Efficient Treatment Against SARS-CoV-2 in hACE2 Mice Conferred by an Intranasal Nanobody (Nb22).

Current COVID-19 vaccines need to take at least one month to complete inoculation and then become effective. Around 51% of the global population is still not fully vaccinated. Instantaneous protection is an unmet need among those who are not fully vaccinated. In addition, breakthrough infections caused by SARS-CoV-2 are widely reported. All these highlight the unmet needing for short-term instantaneous prophylaxis (STIP) in the communities where SARS-CoV-2 is circulating. Previously, we reported nanobodies isolated from an alpaca immunized with the spike protein, exhibiting ultrahigh potency against SARS-CoV-2 and its variants. Herein, we found that Nb22, among our previously reported nanobodies, exhibited ultrapotent neutralization against Delta variant with an IC50 value of 0.41 ng/ml (5.13 pM). Furthermore, the crystal structural analysis revealed that the binding of Nb22 to WH01 and Delta RBDs both effectively blocked the binding of RBD to hACE2. Additionally, intranasal Nb22 exhibited protection against SARS-CoV-2 Delta variant in the post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP). Of note, intranasal Nb22 also demonstrated high efficacy against SARS-CoV-2 Delta variant in STIP for seven days administered by single dose and exhibited long-lasting retention in the respiratory system for at least one month administered by four doses, providing a strategy of instantaneous short-term prophylaxis against SARS-CoV-2. Thus, ultrahigh potency, long-lasting retention in the respiratory system and stability at room-temperature make the intranasal or inhaled Nb22 to be a potential therapeutic or STIP agent against SARS-CoV-2.

A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration.

The dramatically expanding coronavirus disease 2019 (COVID-19) needs multiple effective countermeasures. Neutralizing nanobodies (Nbs) are a potential therapeutic strategy for treating COVID-19. Here, we characterize several receptor binding domain (RBD)-specific Nbs isolated from an Nb library derived from an alpaca immunized with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S); among them, three Nbs exhibit picomolar potency against SARS-CoV-2 live virus, pseudotyped viruses, and circulating SARS-CoV-2 variants. To improve their efficacy, various configurations of Nbs are engineered. Nb15-NbH-Nb15, a trimer constituted of three Nbs, is constructed to be bispecific for human serum albumin (HSA) and RBD of SARS-CoV-2. Nb15-NbH-Nb15 exhibits single-digit ng/ml neutralization potency against the wild-type and Delta variants of SARS-CoV-2 with a long half-life in vivo. In addition, we show that intranasal administration of Nb15-NbH-Nb15 provides effective protection for both prophylactic and therapeutic purposes against SARS-CoV-2 infection in transgenic hACE2 mice. Nb15-NbH-Nb15 is a potential candidate for both the prevention and treatment of SARS-CoV-2 through respiratory administration.

Challenges for Obstetricians and the Countermeasures of COVID-19 Epidemic.

Since the outbreak of the novel coronavirus in Wuhan, China, as obstetricians, we also face great challenges. We need to identify pregnant patients with 2019 coronavirus disease infection timely, and give them appropriate treatment in order to obtain a good maternal and infant prognosis. Here, we would like to share a case and provide some suggestions on how to screen, diagnose and treat pregnant women with 2019 coronavirus disease infection during the outbreak.

Correlation between ground-glass opacity on pulmonary CT and the levels of inflammatory cytokines in patients with moderate-to-severe COVID-19 pneumonia.

Objectives: Comparative analysis of laboratory data in moderate-to-severe COVID-19 patients presenting with or without ground-glass opacities (GGOs). Methods: This retrospective study examined 61 patients with moderate-to-severe COVID-19, as defined by the report of the WHO-China Joint Mission on COVID-19. All patients were admitted to the Department of Infectious Diseases, Wuhan Union Hospital from Dec 28, 2019 to Feb 22, 2020 and classified into a GGO group or a non-GGO group based on CT results. The clinical characteristics and laboratory data of the two groups were compared. Data were analyzed using univariate and multivariate analysis, and using receiver operating characteristic (ROC) analysis. Results: Forty-five patients were in the GGO group (73.8%, 21 females, 24 males, mean age 54.8±17.8 years) and 16 were in the non-GGO group (26.2%, 11 females, 5 males, mean age 53±14.9 years). The levels of IL-2, IL-4, and IFN-γ were greater in the GGO group (all P<0.05). ROC analysis indicated that an elevated level of IL-2 was a good predictor of GGO (area under the curve: 0.716, optimal cutoff: 3.205 pg/mL, 53.8% sensitivity, 87.5% specificity, p<0.05). Multivariate analysis showed that IL-2 level was a significant and independent risk factor for lung GGO (OR: 8.167; 95% CI: 1.63, 40.8; P<0.05). Conclusions: There were correlations between GGO in the lungs of patients with moderate-to-severe COVID-19 and the levels of IL-2, IL-4, and INF-γ. IL-2 was a significant and independent risk factor for GGO. These findings provide a basis for studying the mechanism of pulmonary lesions in COVID-19 patients.

Infants Born to Mothers With a New Coronavirus (COVID-19).

A novel viral respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for an epidemic of the coronavirus disease 2019 (COVID-19) in cases in China and worldwide. Four full-term, singleton infants were born to pregnant women who tested positive for COVID-19 in the city of Wuhan, the capital of Hubei province, China, where the disease was first identified. Of the three infants, for who consent to be diagnostically tested was provided, none tested positive for the virus. None of the infants developed serious clinical symptoms such as fever, cough, diarrhea, or abnormal radiologic or hematologic evidence, and all four infants were alive at the time of hospital discharge. Two infants had rashes of unknown etiology at birth, and one had facial ulcerations. One infant had tachypnea and was supported by non-invasive mechanical ventilation for 3 days. One had rashes at birth but was discharged without parental consent for a diagnostic test. This case report describes the clinical course of four live born infants, born to pregnant women with the COVID-19 infection.