Serum neutralization of SARS-CoV-2 Omicron BA.2, BA.2.75, BA.2.76, BA.5, BF.7, BQ.1.1 and XBB.1.5 in individuals receiving Evusheld (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is undergoing continuous evolution and convergent mutation, which has led to the rapid emergence of several new variants. These new subvariants carry different mutations in theirreceptor-binding domain (RBD), raising concerns that they may evade neutralizing monoclonal antibodies (mAbs). In this study, we investigated the serum neutralization efficacy of Evusheld (cilgavimab and tixagevimab) antibody cocktails against SARS-CoV-2 Omicron sublineages BA.2, BA.2.75, BA.2.76, BA.5, BF.7, BQ.1.1 and XBB.1.5. Our results show that Evusheld retained neutralizing activity against BA.2, BA.2.75 and BA.5, albeit with somewhat reduced titers. However, the neutralizing activity of Evusheld against BA.2.76, BF.7, BQ.1.1 and XBB.1.5 significantly decreased, with XBB.1.5 showing the greatest escape activity among the subvariants, followed by BQ.1.1, BA.2.76 and BF.7. We also observed that recipients of Evusheld displayed elevated antibody levels in their serum, which efficiently neutralized the original variant, and exhibited different characteristics of infection than those who did not receive Evusheld. These findings provide important guidance for the application of Evusheld in treating SARS-CoV-2 subvariant infections.

Reduced sensitivity of SARS-CoV-2 Omicron variant to booster-enhanced neutralization (preprint)

The Omicron Variant of Concern (B.1.1.529) has spread internationally and is raising serious concerns about reduced vaccine efficacy and the increased risk of reinfection. We assessed the serum neutralizing activity using a pseudovirus-based neutralization assay in 292 healthcare workers who had received a homologous booster dose of BBIBP-CorV vaccine, 8 to 9 months after completing the priming two-dose vaccination schedule, to investigate whether the newly identified Omicron variant can escape serum antibody neutralization induced by the booster vaccination. The booster dose of BBIBP-CorV rapidly induced a significantly high level of humoral immune response, and the neutralization geometric mean titer (GMT) against the wild-type strain on day 28 after the booster dose was 294.85 (252.99-343.65), 6.1 times higher than the level on day 28 after the second dose. The neutralization against the Omicron variant was also improved by the booster vaccination, although the GMT showed an approximately 20.1-fold reduction to 14.66 (12.30-17.48) when compared with the wild-type strain. This study demonstrated that a booster dose of BBIBP-CorV led to a significant rebound in neutralizing immune response against SARS-CoV-2, while the Omicron variant showed partial resistance to neutralizing antibodies induced by the booster vaccination.

Neutralizing activity of BBIBP-CorV vaccine-elicited sera against multiple SARS-CoV-2 variants of concern (preprint)

We assessed the safety and immunogenicity of an inactivated SARS-CoV-2 vaccine BBIBP-CorV, especially measured the resistance of four global variants of concern: Lineage B.1.1.7, Lineage B.1.351, Lineage P.1, and Lineage B.1.526 to neutralizing activity of vaccine-elicited sera. Among 1006 enrolled participants, no serious adverse event was reported within 28 days post-vaccination. Seroconversion of neutralizing antibodies was seen in 698 (91.84%) of 760 healthcare workers, and the geometric mean titres (GMTs) of neutralizing antibody titre was 62.68 (57.02–68.91) after the second immunization. We found that 57 (12.13%), 99 (20.97%), and 114 (24.26%) vaccine-elicited sera showed complete or partial loss of neutralizing activity against lineage B.1.1.7, lineage B.1.526, and lineage P.1, respectively, while 199 (42.34%) vaccine-elicited sera preserved neutralizing activity against lineage B.1.351, albeit at relatively low dilutions. These data indicated that humoral responses against SARS-CoV-2 could be effectively induced in vaccine recipients, although diminished neutralization potency against multiple variants was observed.

Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial (preprint)

Abstract Objectives To assess the efficacy and safety of hydroxychloroquine (HCQ) plus standard-of-care (SOC) compared with SOC alone in adult patients with COVID-19. Design Multicenter, open-label, randomized controlled trial. Setting 16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020. Participants 150 patients hospitalized with laboratory-confirmed COVID-19 were included in the intention to treat analysis. 75 patients were assigned to HCQ plus SOC and 75 to SOC alone. Interventions HCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively). Main outcome measures The primary outcome was whether participants had a negative conversion of SARS-CoV-2 by 28 days, and was analyzed according to the intention-to-treat principle. Adverse events were analyzed in the safety population in which HCQ recipients were participants who actually received at least one dose of HCQ and HCQ non-recipients were those actually managed with SOC alone. Results Among 150 patients, 148 were with mild to moderate disease and 2 were with severe disease. The mean days ({+/-}standard deviation, min to max) from symptoms onset to randomization was 16.6 ({+/-}10.5 days, 3 to 41 days). The negative conversion probability by 28 days in SOC plus HCQ group was 85.4% (95% confidence interval (CI) 73.8% to 93.8%), similar to that in the SOC group 81.3% (95%CI 71.2% to 89.6%). Between-group difference was 4.1% (95%CI -10.3% to 18.5%). In the safety population, adverse events were recorded in 7 (8.8%) HCQ non-recipients (N=80) and in 21 (30%) HCQ recipients (N=70). The most common adverse event in the HCQ recipients was diarrhea, reported in 7 (10%) patients. Two HCQ recipients reported serious adverse events. Conclusions The administration of HCQ did not result in a significantly higher negative conversion probability than SOC alone in patients mainly hospitalized with persistent mild to moderate COVID-19. Adverse events were higher in HCQ recipients than in HCQ non-recipients. Trial registration ChiCTR2000029868

Improved deep learning model for differentiating novel coronavirus pneumonia and influenza pneumonia (preprint)

Background: Chest CT had high sensitivity in diagnosing novel coronavirus pneumonia (NCP) at early stage, giving it an advantage over nucleic acid detection in time of crisis. Deep learning was reported to discover intricate structures from clinical images and achieve expert-level performance in medical image analysis. To develop and validate an integrated deep learning framework on chest CT images for auto-detection of NCP, particularly focusing on differentiating NCP from influenza pneumonia (IP). Methods: 35 confirmed NCP cases were consecutively enrolled as training set from 1138 suspected patients in three NCP designated hospitals together with 361 confirmed viral pneumonia patients from center one including 156 IP patients, from May, 2015 to February, 2020. The external validation set enrolled 57 NCP patients and 50 IP patients from eight centers. Results: 96.6% of NCP lesions were larger than 1 cm and 76.8% were with intensity below -500 Hu, indicating less consolidation than IP lesions which had nodules ranging 5-10 mm. The classification schemes accurately distinguished NCP and IP lesions with area under the receiver operating characteristic curve (AUC) above 0.93. The Trinary scheme was more device-independent and consistent with specialists than the Plain scheme, which achieved a F1 score of 0.847, higher than the Plain scheme (0.774), specialists (0.785) and residents (0.644). Conclusions: Our study potentially provides an accurate early diagnosis tool on chest CT for NCP with high transferability, and shows high efficiency in differentiating NCP and IP, helping to reduce misdiagnosis and contain the pandemic transmission.

The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study (preprint)

Currently, there are no approved specific antiviral agents for 2019 novel coronavirus disease (COVID-19). In this study, ten severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 days after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 days. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 days. Several parameters tended to improve as compared to pre-transfusion, including increased lymphocyte counts (0.65*109/L vs. 0.76*109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesionswithin 7 days. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was welltolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.

Clinical Study of Arbidol Hydrochloride Tablets in the Treatment of Pneumonia Caused by Novel Coronavirus