Current status of Guillain-Barré syndrome (GBS) in China: a 10-year comprehensive overview.

Guillain-Barré syndrome (GBS) is an acute inflammatory polyradiculoneuropathy; a disease involving the peripheral nervous system which is the most common cause of acute flaccid paralysis worldwide. So far, it is still lack of a comprehensive overview and understanding of the national epidemiological, clinical characteristics, and the risk factors of GBS in China, as well as differences between China and other countries and regions in these respects. With the global outbreak of the coronavirus disease 2019 (COVID-19), an epidemiological or phenotypic association between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and GBS has attracted great attention. In this review, we outlined the current clinical data of GBS in China by retrieving literature, extracting and synthesizing the data of GBS in China from 2010 to 2021. Besides, we compared the characteristics of epidemiology, preceding events and clinical profiles of GBS between China and other countries and regions. Furthermore, in addition to conventional intravenous immunoglobulin (IVIG) and plasma exchange (PE) therapy, the potential therapeutic effects with novel medications in GBS, such as complement inhibitors, etc., have become the research focus in treatments. We found that epidemiological and clinical findings of GBS in China are approximately consistent with those in the International GBS Outcome Study (IGOS) cohort. We provided an overall picture of the present clinical status of GBS in China and summarized the global research progress of GBS, aiming to further understand the characteristics of GBS and improve the future work of GBS worldwide, especially in countries with the middle and low incomes.

Enhanced evasion of neutralizing antibody response by Omicron XBB.1.5, CH.1.1, and CA.3.1 variants.

Omicron subvariants continuingly challenge current vaccination strategies. Here, we demonstrate nearly complete escape of the XBB.1.5, CH.1.1, and CA.3.1 variants from neutralizing antibodies stimulated by three doses of mRNA vaccine or by BA.4/5 wave infection, but neutralization is rescued by a BA.5-containing bivalent booster. CH.1.1 and CA.3.1 show strong immune escape from monoclonal antibody S309. Additionally, XBB.1.5, CH.1.1, and CA.3.1 spike proteins exhibit increased fusogenicity and enhanced processing compared with BA.2. Homology modeling reveals the key roles of G252V and F486P in the neutralization resistance of XBB.1.5, with F486P also enhancing receptor binding. Further, K444T/M and L452R in CH.1.1 and CA.3.1 likely drive escape from class II neutralizing antibodies, whereas R346T and G339H mutations could confer the strong neutralization resistance of these two subvariants to S309-like antibodies. Overall, our results support the need for administration of the bivalent mRNA vaccine and continued surveillance of Omicron subvariants.

Discovery of novel papain-like protease inhibitors for potential treatment of COVID-19.

The recent emergence of different SARS-CoV-2 variants creates an urgent need to develop more effective therapeutic agents to prevent COVID-19 outbreaks. Among SARS-CoV-2 essential proteases is papain-like protease (SARS-CoV-2 PLpro), which plays multiple roles in regulating SARS-CoV-2 viral spread and innate immunity such as deubiquitinating and deISG15ylating (interferon-induced gene 15) activities. Many studies are currently focused on targeting this protease to tackle SARS-CoV-2 infection. In this context, we performed a phenotypic screening using an in-house pilot compounds collection possessing a diverse skeleta against SARS-CoV-2 PLpro. This screen identified SIMR3030 as a potent inhibitor of SARS-CoV-2. SIMR3030 has been shown to exhibit deubiquitinating activity and inhibition of SARS-CoV-2 specific gene expression (ORF1b and Spike) in infected host cells and possessing virucidal activity. Moreover, SIMR3030 was demonstrated to inhibit the expression of inflammatory markers, including IFN-α, IL-6, and OAS1, which are reported to mediate the development of cytokine storms and aggressive immune responses. In vitro absorption, distribution, metabolism, and excretion (ADME) assessment of the drug-likeness properties of SIMR3030 demonstrated good microsomal stability in liver microsomes. Furthermore, SIMR3030 demonstrated very low potency as an inhibitor of CYP450, CYP3A4, CYP2D6 and CYP2C9 which rules out any potential drug-drug interactions. In addition, SIMR3030 showed moderate permeability in Caco2-cells. Critically, SIMR3030 has maintained a high in vivo safety profile at different concentrations. Molecular modeling studies of SIMR3030 in the active sites of SARS-CoV-2 and MERS-CoV PLpro were performed to shed light on the binding modes of this inhibitor. This study demonstrates that SIMR3030 is a potent inhibitor of SARS-CoV-2 PLpro that forms the foundation for developing new drugs to tackle the COVID-19 pandemic and may pave the way for the development of novel therapeutics for a possible future outbreak of new SARS-CoV-2 variants or other Coronavirus species.

Is there a causal nexus between COVID-19 infection, COVID-19 vaccination, and Guillain-Barré syndrome?

Guillain-Barré syndrome (GBS) is an immune-mediated inflammatory polyradiculoneuropathy, which commonly leads to a very high level of neurological disability. Especially, after the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causation between GBS and SARS-CoV-2 infection and the coronavirus disease 2019 (COVID-19) vaccination have aroused widespread concern. In the review, we analyzed the impacts of SARS-CoV-2 infection and COVID-19 vaccination on GBS globally, aiming to further understand the characteristics of GBS associated with COVID-19. Based on the electrophysiological data, patients suffering from GBS related to COVID-19 manifested as an acute inflammatory demyelinating polyneuropathy (AIDP). Moreover, we summarized the current findings, which may evidence GBS linking to SARS-CoV-2 infection and COVID-19 vaccination, and discussed the underlying mechanisms whether and how the SARS-CoV-2 virus and COVID-19 vaccination can induce GBS and its variants.

STING Agonist-Derived LNP-mRNA Vaccine Enhances Protective Immunity Against SARS-CoV-2.

Lipid nanoparticle (LNP)-mediated delivery of messenger RNA (mRNA) COVID-19 vaccines has provided large-scale immune protection to the public. To elicit a robust immune response against SARS-CoV-2 infections, antigens produced by mRNAs encoding SARS-CoV-2 Spike glycoprotein need to be efficiently delivered and presented to antigen-presenting cells such as dendritic cells (DCs). As concurrent innate immune stimulation can facilitate the antigen presentation process, a library of non-nucleotide STING agonist-derived amino lipids (SALs) was synthesized and formulated into LNPs for mRNA delivery. SAL12 lipid nanoparticles (SAL12-LNPs) were identified as most potent in delivering mRNAs encoding the Spike glycoprotein (S) of SARS-CoV-2 while activating the STING pathway in DCs. Two doses of SAL12 S-LNPs by intramuscular immunization elicited potent neutralizing antibodies against SARS-CoV-2 in mice.

Prime-Pull Immunization of Mice with a BcfA-Adjuvanted Vaccine Elicits Sustained Mucosal Immunity That Prevents SARS-CoV-2 Infection and Pathology.

Vaccines against SARS-CoV-2 that induce mucosal immunity capable of preventing infection and disease remain urgently needed. In this study, we demonstrate the efficacy of Bordetella colonization factor A (BcfA), a novel bacteria-derived protein adjuvant, in SARS-CoV-2 spike-based prime-pull immunizations. We show that i.m. priming of mice with an aluminum hydroxide- and BcfA-adjuvanted spike subunit vaccine, followed by a BcfA-adjuvanted mucosal booster, generated Th17-polarized CD4+ tissue-resident memory T cells and neutralizing Abs. Immunization with this heterologous vaccine prevented weight loss following challenge with mouse-adapted SARS-CoV-2 (MA10) and reduced viral replication in the respiratory tract. Histopathology showed a strong leukocyte and polymorphonuclear cell infiltrate without epithelial damage in mice immunized with BcfA-containing vaccines. Importantly, neutralizing Abs and tissue-resident memory T cells were maintained until 3 mo postbooster. Viral load in the nose of mice challenged with the MA10 virus at this time point was significantly reduced compared with naive challenged mice and mice immunized with an aluminum hydroxide-adjuvanted vaccine. We show that vaccines adjuvanted with alum and BcfA, delivered through a heterologous prime-pull regimen, provide sustained protection against SARS-CoV-2 infection.

Clinical Utility of Circulating Pentraxin 3 as a Prognostic Biomarker in Coronavirus Disease 2019: A Systematic Review and Meta-analysis.

INTRODUCTION: Pentraxin 3 (PTX3) is involved in inflammation regulation and has a certain association with infectious diseases. However, its specific correlation with infectious diseases remains controversial. This study aimed to analyze the association between them and explore the possible role of PTX3 in the prognosis of coronavirus disease 2019 (COVID-19). METHODS: Five databases (PubMed, Cochrane Library, Embase, Clinicaltrials.gov, and gray literature) were searched. Outcomes were expressed as a standardized mean difference (SMD) and 95% confidence intervals (CI). The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of included articles. Stata 12 and Meta-DiSc were applied to analyze the pooled data. Receiver operating characteristic (ROC) curves were conducted to determine the prognostic value of PTX3 for mortality. RESULTS: Six articles met the inclusion criteria. Circulating PTX3 levels had a nonsignificant difference between intensive care unit (ICU) and non-ICU patients with COVID-19 [SMD 1.37 (-0.08, 2.81); I2 = 93.9%, P < 0.01], while the PTX3 levels in nonsurvival COVID-19 patients was significantly lower than those in survival patients [SMD -1.41 (-1.92, -0.91); I2 = 66.4%, P = 0.051]. Circulating PTX3 had good mortality prediction ability (area under ROC curve, AUC = 0.829) in COVID-19. Funnel plots and Egger's tests showed low probabilities of publication bias. Through sensitivity analysis, the results of this study were robust. CONCLUSION: This study found that PTX3 was differentially expressed between survival and nonsurvival patients with COVID-19, while there was no significant difference between ICU and non-ICU patients. Meanwhile, circulating PTX3 may be a good biomarker for monitoring the prognosis of COVID-19, which may provide new ideas and directions for clinical and scientific research.

This study focuses on the relationship between circulating pentraxin 3 (PTX3) and coronavirus disease 2019 (COVID-19). COVID-19 can initiate the inflammatory reaction of the body, trigger a series of immune mechanisms, and cause death in severe cases. PTX3 is a soluble pattern recognition molecule (PRM) belonging to the humoral innate immune system, which may be increasingly deemed as an independent strong prognostic indicator in severe infectious diseases, such as COVID-19. Five databases (Pubmed, Cochrane Library, EMBASE, Clinicaltrials.gov, and gray literature) were searched for six keywords. There was no significant difference in circulating PTX3 levels between intensive care unit (ICU) and non-ICU patients with COVID-19, while the PTX3 levels of nonsurvival patients with COVID-19 was significantly lower than those of survival patients. Circulating PTX3 may indicate good diagnostic value in predicting the mortality of COVID-19, which may be useful as an indicator for monitoring.

Big data and big disaster: a mechanism of supply chain risk management in global logistics industry

PurposeAlthough big data may enhance the visibility, transparency, and responsiveness of supply chains, whether it is effective for improving supply chain performance in a turbulent environment, especially in mitigating the impact of COVID-19, is unclear. The research question the authors addressed is: How do logistics firms improve the supply chain performance in COVID-19 through big data and supply chain integration (SCI)?Design/methodology/approachThe authors used a mixed-method approach with four rounds of data collection. A three-round survey of 323 logistics firms in 26 countries in Europe, America, and Asia was first conducted. The authors then conducted in-depth interviews with 55 logistics firms.FindingsIn the first quantitative study, the authors find mediational mechanisms through which big data analytics technology capability (BDATC) and SCI influence supply chain performance. In particular, BDATC and SCI are two second-order capabilities that help firms develop three first-order capabilities (i.e. proactive capabilities, reactive capabilities, and resource reconfiguration) and eventually lead to innovation capability and disaster immunity that allow firms to survive in COVID-19 and improve supply chain performance. The results of the follow-up qualitative analysis not only confirm the inferences from the quantitative analysis but also provide complementary insights into organizational culture and the institutional environment.Originality/valueThe authors contribute to supply chain risk management by developing a three-level hierarchy of capabilities framework and finding a mechanism with the links between big data and big disaster. The authors also provide managerial implications for logistics firms to address the new management challenges posed by COVID-19.

Selective suppression of de novo SARS-CoV-2 vaccine antibody responses in patients with cancer on B cell-targeted therapy.

We assessed vaccine-induced antibody responses to the SARS-CoV-2 ancestral virus and Omicron variant before and after booster immunization in 57 patients with B cell malignancies. Over one-third of vaccinated patients at the pre-booster time point were seronegative, and these patients were predominantly on active cancer therapies such as anti-CD20 monoclonal antibody. While booster immunization was able to induce detectable antibodies in a small fraction of seronegative patients, the overall booster benefit was disproportionately evident in patients already seropositive and not receiving active therapy. While ancestral virus- and Omicron variant-reactive antibody levels among individual patients were largely concordant, neutralizing antibodies against Omicron tended to be reduced. Interestingly, in all patients, including those unable to generate detectable antibodies against SARS-CoV-2 spike, we observed comparable levels of EBV- and influenza-reactive antibodies, demonstrating that B cell-targeting therapies primarily impair de novo but not preexisting antibody levels. These findings support rationale for vaccination before cancer treatment.

Determinants and Mechanisms of the Low Fusogenicity and High Dependence on Endosomal Entry of Omicron Subvariants.

The rapid spread and strong immune evasion of the SARS-CoV-2 Omicron subvariants has raised serious concerns for the global COVID-19 pandemic. These new variants exhibit generally reduced fusogenicity and increased endosomal entry pathway utilization compared to the ancestral D614G variant, the underlying mechanisms of which remain elusive. Here, we show that the C-terminal S1 mutations of the BA.1.1 subvariant, H655Y and T547K, critically govern the low fusogenicity of Omicron. Notably, H655Y also dictates the enhanced endosome entry pathway utilization. Mechanistically, T547K and H655Y likely stabilize the spike trimer conformation as suggested by increased molecular interactions in structural modeling and enhanced S1 shedding of their reversion mutants K547T and Y655H in viral producer cells. Importantly, the H655Y mutation also determines the low fusogenicity and enhanced dependence on the endosomal entry pathway of other Omicron subvariants, including BA.2, BA.2.12.1, BA.4/5, and BA.2.75. Together, these results uncover mechanisms governing Omicron subvariant entry and provide insights into altered Omicron tissue tropism and pathogenesis. IMPORTANCE Omicron has been shown to predominantly use the endosomal entry pathway, resulting in reduced lung tropism and reduced disease severity; however, the underlying mechanism is not fully understood. In addition, whether the most recent Omicron subvariants, including BA.5 and BA.2.75, use the same pathway as their ancestor for entry is currently not known. In this study, we show that T547K and H655Y mutations in the C terminus of the S1 subunit critically determine the enhanced dependence on the endosomal entry pathway as well as the reduced cell-cell fusion activity of Omicron BA.1, BA.1.1, and other subvariants. Further experiments and molecular modeling suggest that H655Y and K547T stabilize the spike trimer conformation, likely contributing to the decreased fusogenicity and endosomal entry. Our work uncovers novel mechanisms underlying the distinct entry pathway of Omicron subvariants and advances our understanding of their biological characteristics.

Enhanced neutralization resistance of SARS-CoV-2 Omicron subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2.

The continued evolution of SARS-CoV-2 has led to the emergence of several new Omicron subvariants, including BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2. Here, we examine the neutralization resistance of these subvariants against sera from 3-dose vaccinated healthcare workers, hospitalized BA.1-wave patients, and BA.4/5-wave patients. We found enhanced neutralization resistance in all new subvariants, especially in the BQ.1 and BQ.1.1 subvariants driven by N460K and K444T mutations, as well as the BA.2.75.2 subvariant driven largely by its F486S mutation. All Omicron subvariants maintained their weakened infectivity in Calu-3 cells, with the F486S mutation driving further diminished titer for the BA.2.75.2 subvariant. Molecular modeling revealed the mechanisms of antibody-mediated immune evasion by R346T, K444T, F486S, and D1199N mutations. Altogether, these findings shed light on the evolution of newly emerging SARS-CoV-2 Omicron subvariants.

Evasion of neutralizing antibody responses by the SARS-CoV-2 BA.2.75 variant.

The newly emerged BA.2.75 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant contains 9 additional mutations in its spike (S) protein compared to the ancestral BA.2 variant. Here, we examine the neutralizing antibody escape of BA.2.75 in mRNA-vaccinated and BA.1-infected individuals, as well as the molecular basis underlying functional changes in S. Notably, BA.2.75 exhibits enhanced neutralization resistance over BA.2 but less than the BA.4/5 variant. The G446S and N460K mutations of BA.2.75 are primarily responsible for its enhanced resistance to neutralizing antibodies. The R493Q mutation, a reversion to the prototype sequence, reduces BA.2.75 neutralization resistance. The impact of these mutations is consistent with their locations in common neutralizing antibody epitopes. Further, BA.2.75 shows enhanced cell-cell fusion over BA.2, driven largely by the N460K mutation, which enhances S processing. Structural modeling reveals enhanced receptor contacts introduced by N460K, suggesting a mechanism of potentiated receptor utilization and syncytia formation.

Working in unprecedented times: Intersectionality and women of color in UK higher education in and beyond the pandemic

The ongoing COVID-19 pandemic has exacerbated existing inequalities and inequities. Injustices within the labor market mean that the lives particularly of women of color have been negatively affected by the crisis in multiple ways. Guided by standpoint epistemology, we take an intersectional approach and use autoethnographic methods in which we draw on our personal experiences within the United Kingdom's higher education institutions during the pandemic. We illustrate how institutional decisions, approaches, and policies enacted in the wake of COVID-19 exacerbate inequalities and inequities. Three themes stand out from our experiences: (1) meritocracy and the problem of cumulative (dis)advantage, (2) the lack of racial awareness in management decisions, and (3) the operations of power and silencing. We show that universities justify decisions by deploying discourses of meritocracy and ignoring context and the ways women of color staff are persistently disadvantaged due to structural racism and sexism. We find that universities are likely to indicate that their response policies treat all staff absolutely equally without candidly assessing the intersectional impacts of the pandemic on minority staff, which consequently prevent the achievement of equity. We also describe the ways in which the pandemic exposes cultures of institutional silence and silencing when women of color speak up. We conclude with glimpses of hope for resisting the downward pressures of the pandemic crisis toward cultivating more equitable futures.

Big data and big disaster: a mechanism of supply chain risk management in global logistics industry

Purpose Although big data may enhance the visibility, transparency, and responsiveness of supply chains, whether it is effective for improving supply chain performance in a turbulent environment, especially in mitigating the impact of COVID-19, is unclear. The research question the authors addressed is: How do logistics firms improve the supply chain performance in COVID-19 through big data and supply chain integration (SCI)? Design/methodology/approach The authors used a mixed-method approach with four rounds of data collection. A three-round survey of 323 logistics firms in 26 countries in Europe, America, and Asia was first conducted. The authors then conducted in-depth interviews with 55 logistics firms. Findings In the first quantitative study, the authors find mediational mechanisms through which big data analytics technology capability (BDATC) and SCI influence supply chain performance. In particular, BDATC and SCI are two second-order capabilities that help firms develop three first-order capabilities (i.e. proactive capabilities, reactive capabilities, and resource reconfiguration) and eventually lead to innovation capability and disaster immunity that allow firms to survive in COVID-19 and improve supply chain performance. The results of the follow-up qualitative analysis not only confirm the inferences from the quantitative analysis but also provide complementary insights into organizational culture and the institutional environment. Originality/value The authors contribute to supply chain risk management by developing a three-level hierarchy of capabilities framework and finding a mechanism with the links between big data and big disaster. The authors also provide managerial implications for logistics firms to address the new management challenges posed by COVID-19.

Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination.

SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S-specific total and neutralizing antibody responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19-vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing antibody against D614G, Delta (B.1.617.2), and Omicron BA.1.1 in the BAL compared with COVID-19 convalescents despite robust S-specific antibody responses in the blood. Furthermore, mRNA vaccination induced circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing antibody responses, especially against SARS-CoV-2 Omicron BA.1.1 in mice; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses not only against the ancestral virus but also the Omicron BA.1.1 variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during reinfection, but offer limited protection against breakthrough infection, especially by the Omicron sublineage. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by the Omicron sublineage and future VOCs.

Evasion of Neutralizing Antibody Responses by the SARS-CoV-2 BA.2.75 Variant

The newly emerged BA.2.75 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant contains 9 additional mutations in its spike (S) protein compared to the ancestral BA.2 variant. Here we examine the neutralizing antibody escape of BA.2.75 in mRNA-vaccinated and BA.1-infected individuals, as well as the molecular basis underlying functional changes in S. Notably, BA.2.75 exhibits enhanced neutralization resistance over BA.2, but less than the BA.4/5 variant. The G446S and N460K mutations of BA.2.75 are primarily responsible for its enhanced resistance to neutralizing antibodies. The R493Q mutation, a reversion to the prototype sequence, also reduces BA.2.75 neutralization resistance. The impact of these mutations is consistent with their locations in common neutralizing antibody epitopes. Further, BA.2.75 shows enhanced cell-cell fusion over BA.2, driven largely by the N460K mutation, which enhances S processing. Structural modeling reveals enhanced receptor contacts introduced by N460K, suggesting a mechanism of potentiated receptor utilization and syncytia formation. Newly emerged Omicron subvariants reignite concerns over escape from existing immunity. Qu and colleagues compare the immunity resistance and fusogenicity of BA.2.75 with prior variants. BA.2.75 exhibits stronger neutralization resistance than BA.2 but weaker than BA.4/5, as well as enhanced fusogenicity, which are largely driven by G446S and N460K, respectively.

Clinical Utility of Circulating Pneumoproteins as Diagnostic and Prognostic Biomarkers in COVID-19: A Systematic Review and Meta-analysis.

INTRODUCTION: This study explored circulating pneumoproteins in the diagnosis, severity, and prognosis of COVID-19 by meta-analysis. METHODS: We searched five databases and other sources until December 16, 2021. Standardized mean difference (SMD) and 95% confidence interval (CI) were the overall outcomes. RevMan 5.3, Stata 16, and Meta-DiSc 1.4 were utilized for pooled analysis. RESULTS: A total of 2432 subjects from 26 studies were included. Patients with COVID-19 had higher circulating KL-6, SP-D, and SP-A levels (SMD 1.34, 95% CI [0.60, 2.08]; SMD 1.74, 95% CI [0.64, 2.84]; SMD 3.42, 95% CI [1.31, 5.53], respectively) than healthy individuals. Circulating SP-D levels were not significantly different in survivors and non-survivors (SMD - 0.19, 95% CI [- 0.78, 0.40]). Circulating KL-6, SP-D, and RAGE levels in patients with mild to moderate COVID-19 were significantly lower (SMD - 0.93, 95% CI [- 1.22, - 0.65]; SMD - 1.32, 95% CI [- 2.34, - 0.29]; SMD - 1.17, 95% CI [- 2.06, - 0.28], respectively) than in patients with severe COVID-19. Subgroup analysis suggested that country and total number may be related to the heterogeneity when analyzing SP-D in patients with mild to moderate vs. severe COVID-19. The meta-analysis of diagnostic accuracy including KL-6 for severity, KL-6 for mortality, and SP-D for severity demonstrated that they all had limited diagnostic value. CONCLUSION: Therefore, circulating pneumoproteins (KL-6, SP-D, and RAGEs) reflect the diagnosis, severity, and prognosis of COVID-19, and follow-up studies are still needed.