Humoral immune response characteristics of the susceptible populations after the infection of SARS-CoV-2 BA.5 strain (preprint)

This study compared the humoral immune characteristics of children, elderly people, pregnant women, and adults infected with BA.5 and XBB strains in Guangzhou, China. It was found that binding and neutralizing antibodies the titers against distinct SARS-CoV-2 strains were low in the acute-phase sera of BA.5 infected patients, while the corresponding titers were significantly increased in the convalescent phase, the antibody titers against the Wuhan strain were the highest. Regardless of whether they were vaccinated, BA.5 infection did not induce high neutralizing antibodies against XBB. During the recovery phase, the titers of antiviral antibodies in the vaccinated population are more robust than those in the unvaccinated population. For BA.5 infections, the specific binding and neutralizing antibody titers in the children group were lower compared to other population groups. In the convalescence period of the disease, the titers of neutralizing antibodies against Wuhan, BA.5 and XBB strains induced by BA.5 infections are significantly correlated in pairs. XBB can induce a broader and balanced antiviral humoral immune response than BA.5 as a first-time infected strain. This finding can provide a reference for the judgment of the future epidemic law of SARS-CoV-2, and provide a scientific basis for developing novel COVID-19 vaccines, especially for discovering customized vaccines and immune strategies for different populations.

Assessment of antibody responses against SARS-CoV-2 in unvaccinated individuals and vaccinees from Omicron-BA.2 infection in Zhaoqing, Guangdong Province, China (preprint)

Currently, the majority of the global population has been vaccinated with the COVID-19 vaccine, and characterization studies of antibodies in vivo from Omicron breakthrough infection and naive infection populations are urgently needed to provide pivotal clues about accurate diagnosis, treatment, and next-generation vaccine design against SARS-CoV-2 infection. We showed that after infection with Omicron-BA.2, the antibody levels of specific IgM against the Wuhan strain and specific IgG against Omicron were not significantly elevated within 27 days of onset, Interestingly, in this study, the levels of humoral immunity against Omicron specific IgM were significantly increased after breakthrough infection, suggesting that the detection of Omicron specific IgM antibodies can be used as a test criterion of Omicron breakthrough infection. In addition, we observed that serums from unvaccinated individuals and the majority of vaccinated infections possessed only low or no neutralizing activity against Omicron at the onset of Omicron breakthrough infections, and at the later stage of Omicron-BA.2 breakthrough infection, levels of neutralization antibody against the Wuhan and Omicron strains were elevated in infected individuals. The findings of this study provide important clues for the diagnosis of Omicron breakthrough infections, antibody characterization studies, and the design of next-generation vaccines for COVID-19.

Pulmonary Fibrosis and Its Related Factors in Discharged Patients with New Coronavirus Pneumonia: A Cohort Study of 90-150 Days Follow-Up after Onset (preprint)

Background: The Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic, posing a serious threat to public health worldwide. Whether survivors of COVID-19 pneumonia may be at risk of pulmonary fibrosis is still unknown.Methods: This study involves 462 laboratory confirmed patients with COVID-19 who were admitted to Shenzhen Third People’s Hospital. A total of 457 patients underwent thin-section chest CT scans during the hospitalization or after discharge to identify the pulmonary lesion. A total of 287 patients were followed up from 90 days to 150 days after the onset of the disease.Finding: 397 (86.87%), 311 (74.40%), 222 (79.56%), 141 (68.12%) and 49 (62.03%) patients developed with pulmonary fibrosis during the 0-30, 31-60, 61-90, 91-120 and >120 days after onset, respectively. Reversal of pulmonary fibrosis were found in 18 (4.53%), 61 (19.61%), 40 (18.02%), 54 (38.30%) and 24 (48.98%) COVID-19 patients during the 0-30, 31-60, 61-90, 91-120 and >120 days after onset, respectively. It was observed that Age, BMI, Fever, and Highest PCT were predictive factors for sustaining fibrosis even after 90 days from onset. Only a fraction of COVID-19 patients suffered with abnormal lung function after 90 days from onset.Interpretation: Long-term pulmonary fibrosis was more likely to develop in patients with older age, high BMI, severe/critical condition, fever, long time to turn the viral RNA negative, pre-existing disease and delay to admission. Fibrosis developed in COVID-19 patients could be reversed in about a half of the patients after 120 days from onset. The pulmonary function of most of COVID-19 patients with pulmonary fibrosis could turn to normal condition after three months from onset.Funding Statement: Shenzhen Science and Technology Research and Development Project (202002073000001 and 202002073000002), Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties (SZGSP011).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: This study was conducted at Shenzhen Third People's Hospital and approved by the Ethics Committees, each patient gave written informed consent.

Pulmonary fibrosis and its related factors in discharged patients with new coronavirus pneumonia: A cohort study (preprint)

Background: Thousands of the Coronavirus Disease 2019 (COVID-19) patients have been discharged from hospitals, persistent follow-up studies are required to evaluate the prevalence of post-COVID-19 fibrosis.Methods: This study involves 462 laboratory confirmed patients with COVID-19 who were admitted to Shenzhen Third People’s Hospital from January 11, 2020 to April 26, 2020. A total of 457 patients underwent thin-section chest CT scans during the hospitalization or after discharge to identify the pulmonary lesion. A total of 287 patients were followed up from 90 days to 150 days after the onset of the disease, and lung function tests were conducted in about three months after the onset. The risk factors affecting the persistence of pulmonary fibrosis were identified through regression analysis and the prediction model of the persistence of pulmonary fibrosis was established.Results:  Parenchymal bands, irregular interfaces, reticulation and traction bronchiectasis were the most common CT features in all COVID-19 patients. During the 0-30, 31-60, 61-90, 91-120 and >120 days after onset, 86.87%, 74.40%, 79.56%, 68.12% and 62.03% patients developed with pulmonary fibrosis and 4.53%, 19.61%, 18.02%, 38.30% and 48.98% patients reversed pulmonary fibrosis, respectively. It was observed that Age, BMI, Fever, and Highest PCT were predictive factors for sustaining fibrosis even after 90 days from onset. A predictive model of the persistence with pulmonary fibrosis was developed based-on the Logistic Regression method with an accuracy, PPV, NPV, Sensitivity and Specificity of the model of 76%, 71%, 79%, 67%, and 82%, respectively. More than half of COVID-19 patients revealed abnormal condition in lung function after 90 days from onset, and the ratio of abnormal lung function did not differ on a statistically significant level between the fibrotic and non-fibrotic groups.Conclusions: Persistent pulmonary fibrosis was more likely to develop in patients with older age, high BMI, severe/critical condition, fever, long time to turn the viral RNA negative, pre-existing disease and delay to admission. Fibrosis developed in COVID-19 patients could be reversed in about a third of the patients after 120 days from onset. The pulmonary function of less than half of COVID-19 patients could turn to normal condition after three months from onset. An effective prediction model with an average Area Under the Curve (AUC) of 0.84 was established to predict the persistence of pulmonary fibrosis in COVID-19 patients for early diagnosis.

A non-competing pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2 (preprint)

Neutralizing antibodies could be antivirals against COVID-19 pandemics. Here, we report the isolation of four human-origin monoclonal antibodies from a convalescent patient in China. All of these isolated antibodies display neutralization abilities in vitro. Two of them (B38 and H4) block the binding between RBD and vial cellular receptor ACE2. Further competition assay indicates that B38 and H4 recognize different epitopes on the RBD, which is ideal for a virus-targeting mAb-pair to avoid immune escape in the future clinical applications. Moreover, therapeutic study on the mouse model validated that these two antibodies can reduce virus titers in the infected mouse lungs. Structure of RBD-B38 complex revealed that most residues on the epitope are overlapped with the RBD-ACE2 binding interface, which explained the blocking efficacy and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide the structural basis of rational vaccine design. One Sentence SummaryA pair of human neutralizing monoclonal antibodies against COVID-19 compete cellular receptor binding but with different epitopes, and with post-exposure viral load reduction activity.

Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome (preprint)

The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, December 2019, and continuously poses a serious threat to public health. Our previous study has shown that cytokine storm occurred during SARS-CoV-2 infection, while the detailed role of cytokines in the disease severity and progression remained unclear due to the limited case number. In this study, we examined 48 cytokines in the plasma samples from 53 COVID-19 cases, among whom 34 were severe cases, and the others moderate. Results showed that 14 cytokines were significantly elevated upon admission in COVID-19 cases. Moreover, IP-10, MCP-3, and IL-1ra were significantly higher in severe cases, and highly associated with the PaO2/FaO2 and Murray score. Furthermore, the three cytokines were independent predictors for the progression of COVID-19, and the combination of IP-10, MCP-3 and IL-1ra showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations. Serial detection of IP-10, MCP-3 and IL-1ra in 14 severe cases showed that the continuous high levels of these cytokines were associated with disease deterioration and fatal outcome. In conclusion, we report three cytokines that closely associated with disease severity and outcome of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, which suggested novel therapeutic targets and strategy.

Laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections (preprint)

Background: The outbreak of novel coronavirus pneumonia (NCP) caused by 2019-nCoV spread rapidly, and elucidation the diagnostic accuracy of different respiratory specimens is crucial for the control and treatment of this diseases. Methods: Respiratory samples including nasal swabs, throat swabs, sputum and bronchoalveolar lavage fluid (BALF) were collected from Guangdong CDC confirmed NCP patients, and viral RNAs were detected using a CFDA approved detection kit. Results were analyzed in combination with sample collection date and clinical information. Finding: Except for BALF, the sputum possessed the highest positive rate (74.4%~88.9%), followed by nasal swabs (53.6%~73.3%) for both severe and mild cases during the first 14 days after illness onset (d.a.o). For samples collected [≥] 15 d.a.o, sputum and nasal swabs still possessed a high positive rate ranging from 42.9%~61.1%. The positive rate of throat swabs collected [≥] 8 d.a.o was low, especially in samples from mild cases. Viral RNAs could be detected in all the lower respiratory tract of severe cases, but not the mild cases. CT scan of cases 02, 07 and 13 showed typical viral pneumonia with ground glass opacity, while no viral RNAs were detected in first three or all the upper respiratory samples. Interpretation: Sputum is most accurate for laboratory diagnosis of NCP, followed by nasal swabs. Detection of viral RNAs in BLAF is necessary for diagnosis and monitoring of viruses in severe cases. CT scan could serve as an important make up for the diagnosis of NCP. Funding National Science and Technology Major Project, Sanming Project of Medicine and China Postdoctoral Science Foundation.