Recent developments in the immunopathology of COVID-19 (preprint)

There has been an important change in the clinical characteristics and immune profile of COVID-19 patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID-19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID-19. The efficacy COVID-19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4 and BA.5 and the global administration of COVID-19 vaccines have changed the clinical scenario of COVID-19. Multisystem inflammatory syndrome in children (MIS-C) has been identified as an important cause of death of children with COVID-19. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long-term symptoms of COVID-19. Atopic diseases, such as allergic asthma and rhinitis, have been shown to be associated with a lower susceptibility and better outcomes of COVID-19. At the beginning of pandemic, EAACI developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID-19 vaccines and emerging SARS-CoV-2 variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID-19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID-19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID-19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS-CoV-2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high-risk groups, the development of MIS-C and long COVID.

Depicting the innate immune response landscape in Covid-19 emphasized type 1 interferon a key defense against SARS-CoV-2 (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rampantly threatening much more people life, thus timely and precise countermeasures against SARS-COV-2 were a matter of urgency. Here, integrated bio-information analyse were used for deeply understanding the process of SARS-COV-2 infection. And it was demonstrated that pathways related to antivirus response, innate immune response, and type 1 interferon pathways were dominantly enriched in Covid-19, while neutrophil degranulation, inflammatory reaction and Covid-19 adverse outcome were also assigned significance. PPI network revealed that type 1 interferon pathways related genes ranked as the hub genes in Covid-19, and among these genes OASL, IFIT1,IFIT2,IFIT3 might be typically drug targeted, which was demonstrated by the cerna network and drug interaction network. Our research in the end meant to fundamentally achieve recommended strategies to benefit people suffering from SARS-COV-2 infection.

Delta infection following vaccination elicits potent neutralizing immunity against the SARS-CoV-2 Omicron (preprint)

Since the initial detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) in November 2021 in South Africa, it has caused a rapid increase in infections globally. The Omicron variant encodes 37 amino acid substitutions in its spike protein, and early reports have provided evidence for extensive immune escape and reduced vaccine effectiveness. We assessed serum neutralizing activity in sera from Delta infection following vaccination of CoronaVac or ZF2001 and Delta infection only against SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, Delta, and Omicron. We found that sera from Delta infection only could neutralize WA1 and Delta pseudoviruses but nearly completely lost capacity to neutralize Beta and Omicron pseudoviruses. However, Delta infection following vaccination resulted in a significant increase of serum neutralizing activity against WA1, Beta, and Omicron. This study demonstrates that breakthrough infection of Delta in previously vaccinated individuals substantially induced high potency humoral immune response against the Omicron variant and other emerged variants.

The Efficacy and Safety of Bamlanivimab Treatment Against COVID-19：A Meta-Analysis (preprint)

Background: Bamlanivimab is routinely used in the treatment of coronavirus disease 2019 (COVID-19) in worldwide. We performed a meta-analysis to investigate the efficacy and safety of bamlanivimab treatment in patients with COVID-19. Methods: We searched articles from Web of Science, PubMed, Embase, the Cochrane Library and MedRxiv between 30 January 2020 and August 5, 2021. We selected randomized clinical trials (RCTs) and observational studies with a control group to assess the efficiency of bamlanivimab in treating patients with COVID-19. Results: Our meta-analysis retrieved 3 RCTs and 7 cohort studies including 14461 patients. Bmlanivimab may help outpatients to prevent hospitalization or emergency department visit (RR 0.41 95%CI 0.29 to 0.58), reduce ICU admission (RR 0.47 95%CI 0.23 to 0.92) and mortality (RR 0.32 95%CI 0.13 to 0.77) from the disease. The combination of bamlanivimab and etesevimab may had a greater potential for positive treatment outcome. Conclusion: Bamlanivimab has demonstrated clinical efficacy on mild or moderate ill patients with COVID-19 to prevent hospitalization, reduce severity and mortality from the disease . Combinations of two or more monoclonal antibody increase the effect. Well-designed clinical trials to identify the clinical and biochemical characteristics in COVID-19 patients’ population that could benefit from bamlanivimab are warranted in the future.Funding Statement: None to declare. Declaration of Interests: The authors declared there are no competing interests.

High Expression of ACE2 and TMPRSS2 at the Resection Margin Makes Lung Cancer Survivors Susceptible to SARS-CoV-2 with Unfavorable Prognosis (preprint)

Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide. Systematic analysis of lung cancer survivors at molecular and clinical levels is warranted to understand the disease course and clinical characteristics. We performed a retrospective study of 65 patients with COVID-19 from Wuhan Huoshenshan Hospital, of which 13 patients were diagnosed with lung cancer. Duringtreatment, lung cancer survivors infected with severe acute respiratory syndrome coronavirus 2 had a shorter median time from symptom onset to hospitalization (P=0.016) and longer clinical symptom remission time (P=0.020) than non-cancer individuals. No differences were observed among indicators such as time from symptom onset to hospitalization and symptom remission time between long-term and short-term survivors. The expression of ACE2(P=0.013) and TMPRSS2(P<0.001) was elevated in lung cancer survivors as compared with that in non-cancer individuals.

Association of CT Findings with clinical severity in Patients with COVID-19, a multicenter Cohort observational study (preprint)

Background 2019 Novel Coronavirus disease (COVID-19) may cause critical illness including severe pneumonia and acute respiratory distress syndrome. Our purpose is to was to analyze the radiological features of COVID-19 pneumonia and its association with clinical severity.Methods This retrospective study included 212 patients (122 males, Mean age, 45.6 ± 12.8 years) from 10 hospitals. Chest CT, chest X-ray (CXR), clinical and laboratory data at admission and follow-up CT were collected. Chest CT and CXR were reviewed and CT score of the involved lung was calculated.Results 94.3% patients had pneumonia on the baseline CT at admission. The most CT findings were as follows: GGO (140/200), GGO with consolidation (38/200) and consolidation (16/200) most involving the lower lobes with a predilection for the peripheral aspects. The CT score negatively correlated with Lymphocyte count while it positively correlated with C-reactive protein. ROC curve showed an optimal cutoff value of the CT score of 15 had a sensitivity of 70% and a specificity of 96.5% for the prediction of severe status. Series CT showed GGO or consolidation gradually reduced in 52 patients while 6 patients had reticular opacities. 14 patients showed the normal CXR while GGO were found on CT.Conclusion COVID-19 pneumonia manifests as focal, multifocal ground-glass opacities with/without consolidations. Higher CT score correlated severe clinical status. CXR is yet insufficient for evaluation of COVID-19 pneumonia.

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.

New coronavirus pneumonia COVID-19 and ocular surface transmission / 国际眼科杂志(Guoji Yanke Zazhi)

@#Since the end of 2019, the novel coronavirus pneumonia(COVID-19)has rapidly spread in Wuhan City, Hubei Province of China. This has aroused great concern of the Chinese government and the international community. There have been unconfirmed threads of COVID-19 patients with conjunctivitis as the first symptom. Therefore, the issue that whether and how the novel coronavirus strain SARS-CoV-2 infection is transmitted through the ocular surface has become a new concern. In the absence of clinical and experimental evidence of COVID-19 in ocular infection, we have conducted a retrospective literature analysis of viral pathogens that simultaneously trigger ocular lesions during the onset of epidemic diseases. The purpose of this paper is to provide some reference and suggestions for appropriately understanding of ocular protection in the prevention and control of the COVID-19.