The practice of drug emergency supply in China from a policy mix perspective (preprint)

Background This study aims to analyze relevant policy texts, explore and determine the focal points and inadequacies of the Chinese government in guaranteeing supplies of medicines, and provide advice on how to make better policies about drug supply when public health emergencies occur.Methods We selected 559 documents that guided the support of drug supply during emergencies issued by governments at both the national and provincial levels from December 1, 2019, to February 28, 2023. In addition, we developed a four-dimensional analysis framework of the issuing agency, issuing period, policy tools, and drug supply chain to analyze specific policy items, determine their basic characteristics, and quantitatively analyze them from a policy mix perspective.Results The analysis using policy tools showed that the national government tended to call on stakeholders in all aspects of drug supply to fulfil their responsibilities, and both national and provincial governments tended to use incentive tools, such as opening up urgent drug supply tracks and applying financial incentives to promote drug supply. However, managing stakeholders’ behaviors in drug supply and the capacity building to guarantee drug supply are still lacking and require improvement. From the perspective of the drug supply chain, the national government has paid much attention to the distribution of drugs, whereas attention to the supply of drug substances has been lacking. As various stages of the COVID-19 pandemic, the number of policies related to drug supply increased slowly after a surge at the beginning of the pandemic and then rapidly decreased. From the policy mix perspective, the analysis showed that incentives were lacking in drug research and development, and capacity building was not discussed much in the drug manufacturing process.Conclusions We suggest enhancing the complementarity and cohesion of the policy content issued by national and provincial governments, strengthening the coordination and connection between policymaking bodies, optimizing the internal structure of policy tools, improving the performance of various policy strategies, and using appropriate policy tools to create policies suited to various stages of emergencies and drug supply chains.

Meaning in stressful experiences and coping across cultures

We report three studies to examine how culture may influence people's tendency to see meaning in stressful experiences (MISE), as well as their coping responses. Using a newly developed MISE scale with established measurement invariance across both cultures, we found that Chinese participants were more likely than Euro-Canadians to see meaning in stressful experiences (Studies 1 and 2), to adopt acceptance and positive reframing coping styles (Study 1), and to respond more positively to the COVID-19 pandemic (Study 2). To establish a causal link between MISE and coping, we primed MISE in Study 3 with Chinese participants and found an increase in resilient coping. The research highlights the important roles of culture and meaning making in coping. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

An Online Survey on the Relationship Between Positive Coping and Post-Traumatic Stress Symptoms (PTSS) of Medical Students in China During the COVID-19 Pandemic: The Mediating Role of Social Support.

BACKGROUND The COVID-19 pandemic has caused varying degrees of psychological stress among medical students. This research explored the post-traumatic stress symptoms (PTSS) of medical students in China and their relationship with positive coping and social support. MATERIAL AND METHODS In the form of cross-sectional online survey, 2280 medical students locked down at home were selected by random cluster method to investigate social support, coping style, and PTSS using the Social Support Rating Scale (SSRS), Simplified Coping Style Questionnaire (SCSQ), and Post-traumatic Stress Disorder (PTSD) Checklist-Civilian Version (PCL-C), respectively. RESULTS This research found that the PTSS detection rate in medical students was 10.42% during the COVID-19 pandemic. The PTSS scores of females were significantly higher than that of the males. However, the PTSS detection rate in females (9.71%) was not significantly different from that in males (11.24%). Compared with those of the non-PTSS group, the total score and its all-factor score of social support, the total score of coping style and the positive coping score of the PTSS group were much lower, while the negative coping score of the PTSS group was much higher (P<0.01). Positive coping was positively correlated with social support, while positive coping and social support were negatively correlated with PTSS. The total effect of positive coping on PTSS was -0.310 (P<0.001), the direct effect was -0.128 (P<0.01), and the indirect effect was -0.182 (P<0.001). Social support played a mediating role between positive coping and PTSS, with the mediating effect accounting for 58.81% of the total effect. CONCLUSIONS Social support plays a mediating role between positive coping and post-traumatic stress symptoms. Objective support and positive coping are the 2 main protective factors of PTSS.

Gasdermin D-mediated pyroptosis: mechanisms, diseases, and inhibitors.

Gasdermin D (GSDMD)-mediated pyroptosis and downstream inflammation are important self-protection mechanisms against stimuli and infections. Hosts can defend against intracellular bacterial infections by inducing cell pyroptosis, which triggers the clearance of pathogens. However, pyroptosis is a double-edged sword. Numerous studies have revealed the relationship between abnormal GSDMD activation and various inflammatory diseases, including sepsis, coronavirus disease 2019 (COVID-19), neurodegenerative diseases, nonalcoholic steatohepatitis (NASH), inflammatory bowel disease (IBD), and malignant tumors. GSDMD, a key pyroptosis-executing protein, is linked to inflammatory signal transduction, activation of various inflammasomes, and the release of downstream inflammatory cytokines. Thus, inhibiting GSDMD activation is considered an effective strategy for treating related inflammatory diseases. The study of the mechanism of GSDMD activation, the formation of GSDMD membrane pores, and the regulatory strategy of GSDMD-mediated pyroptosis is currently a hot topic. Moreover, studies of the structure of caspase-GSDMD complexes and more in-depth molecular mechanisms provide multiple strategies for the development of GSDMD inhibitors. This review will mainly discuss the structures of GSDMD and GSDMD pores, activation pathways, GSDMD-mediated diseases, and the development of GSDMD inhibitors.

ACE2 negatively regulates the Warburg effect and suppresses hepatocellular carcinoma progression via reducing ROS-HIF1α activity.

Aerobic glycolysis has pleiotropic roles in the pathogenesis of hepatocellular carcinoma (HCC). Emerging studies revealed key promoters of aerobic glycolysis, however, little is known about its negative regulators in HCC. In this study, an integrative analysis identifies a repertoire of differentially expressed genes (DNASE1L3, SLC22A1, ACE2, CES3, CCL14, GYS2, ADH4, and CFHR3) that are inversely associated with the glycolytic phenotype in HCC. ACE2, a member of the rennin-angiotensin system, is revealed to be downregulated in HCC and predicts a poor prognosis. ACE2 overexpression significantly inhibits the glycolytic flux as evidenced by reduced glucose uptake, lactate release, extracellular acidification rate, and the expression of glycolytic genes. Opposite results are noticed in loss-of-function studies. Mechanistically, ACE2 metabolizes Ang II to Ang-(1-7), which activates Mas receptor and leads to the phosphorylation of Src homology 2-containing inositol phosphatase 2 (SHP-2). SHP2 activation further blocks reactive oxygen species (ROS)-HIF1α signaling. Addition of Ang-(1-7) or the antioxidant N-acetylcysteine compromises in vivo additive tumor growth and aerobic glycolysis induced by ACE2 knockdown. Moreover, growth advantages afforded by ACE2 knockdown are largely glycolysis-dependent. In clinical settings, a close link between ACE2 expression and HIF1α or the phosphorated level of SHP2 is found. Overexpression of ACE2 significantly retards tumor growth in patient-derived xenograft model. Collectively, our findings suggest that ACE2 is a negative glycolytic regulator, and targeting the ACE2/Ang-(1-7)/Mas receptor/ROS/HIF1α axis may be a promising therapeutic strategy for HCC treatment.

A Nomogram for Predicting Delayed Viral Shedding in Non-Severe SARS-CoV-2 Omicron Infection.

Purpose: The Omicron variant of SARS-CoV-2 has emerged as a significant global concern, characterized by its rapid transmission and resistance to existing treatments and vaccines. However, the specific hematological and biochemical factors that may impact the clearance of Omicron variant infection remain unclear. The present study aimed to identify easily accessible laboratory markers that are associated with prolonged virus shedding in non-severe patients with COVID-19 caused by the Omicron variant. Patients and Methods: A retrospective cohort study was conducted on 882 non-severe COVID-19 patients who were diagnosed with the Omicron variant in Shanghai between March and June 2022. The least absolute shrinkage and selection operator regression model was used for feature selection and dimensional reduction, and multivariate logistic regression analysis was performed to construct a nomogram for predicting the risk of prolonged SARS-CoV-2 RNA positivity lasting for more than 7 days. The receiver operating characteristic (ROC) curve and calibration curves were used to assess predictive discrimination and accuracy, with bootstrap validation. Results: Patients were randomly divided into derivation (70%, n = 618) and validation (30%, n = 264) cohorts. Optimal independent markers for prolonged viral shedding time (VST) over 7 days were identified as Age, C-reactive protein (CRP), platelet count, leukocyte count, lymphocyte count, and eosinophil count. These factors were subsequently incorporated into the nomogram utilizing bootstrap validation. The area under the curve (AUC) in the derivation (0.761) and validation (0.756) cohorts indicated good discriminative ability. The calibration curve showed good agreement between the nomogram-predicted and actual patients with VST over 7 days. Conclusion: Our study confirmed six factors associated with delayed VST in non-severe SARS-CoV-2 Omicron infection and constructed a Nomogram which may assist non-severely affected patients to better estimate the appropriate length of self-isolation and optimize their self-management strategies.

Pausing transplants in the face of a global pandemic: Patient survival implications.

The coronavirus disease 2019 (COVID-19) pandemic has disrupted normal operating procedures at transplant centers. With the possibility that COVID-19 infection carries an overall 4% mortality rate and potentially a 24% mortality rate among the immunocompromised transplant recipients, many transplant centers considered the possibility of slowing down and even potentially pausing all transplants. Many proposals regarding the need for pausing organ transplants exist; however, much remains unknown. Whereas the impact of the COVID-19 pandemic on the overall healthcare system is unknown, the potential impact of pausing organ transplants over a period can be estimated. This study presents a model for evaluating the impact of pausing liver transplants over a spectrum of model for end-stage liver disease-sodium (MELD-Na) scores. Our model accounts for two potential risks of a pause: (1) the waitlist mortality of all patients who do not receive liver transplants during the pause period, and (2) the impact of a longer waiting list due to the pause of liver transplants and the continuous accrual of new patients. Using over 12 years of liver transplant data from the United Network for Organ Sharing and a system of differential equations, we estimate the threshold probability above which a decision maker should pause liver transplants to reduce the loss of patient life months. We also compare different pause policies to illustrate the value of patient-specific and center-specific approaches. Finally, we analyze how capacity constraints affect the loss of patient life months and the length of the waiting list. The results of this study are useful to decision makers in deciding whether and how to pause organ transplants during a pandemic. The results are also useful to patients (and their care providers) who are waiting for organ transplants.

eHealth Literacy of Chinese Residents During the Coronavirus Disease 2019 Pandemic: A Cross-sectional Survey.

The Coronavirus Disease 2019 (COVID-19) pandemic has become a leading societal concern. eHealth literacy is important in the prevention and control of this pandemic. The purpose of this study is to identify eHealth literacy of Chinese residents about the COVID-19 pandemic and factors influencing eHealth literacy. A total of 15 694 individuals clicked on the link to the questionnaire, and 15 000 agreed to participate and completed the questionnaire for a response rate of 95.58%. Descriptive statistics, χ2 test, and logistic regression analysis were conducted to analyze participants' level of eHealth literacy about COVID-19 and its influencing factors. The results showed 52.2% of participants had relatively lower eHealth literacy regarding COVID-19 (eHealth literacy score ≤ 48). The scores of the information judgment dimension (3.09 ± 0.71) and information utilization dimension (3.18 ± 0.67) of the eHealth literacy scale were relatively lower. The logistics regression showed that sex, age, education level, level of uncertainty, having people around the respondent diagnosed with COVID-19, relationship with family, and relationship with others were associated to eHealth literacy (χ2 = 969.135, P < .001). The public's eHealth literacy about COVID-19 needs to be improved, especially the ability to judge and utilize online information. Close collaboration among global health agencies, governments, healthcare institutions, and media is needed to provide reliable online information to the public. Interventions to improve eHealth literacy should take into account and accentuate the importance of sex, age, educational background, level of uncertainty, exposure to disease, and social support.

Clinicopathological and immunological features of new onset kidney disease: a rare event after SARS-CoV-2 vaccination.

The onset of various kidney diseases has been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, detailed clinical and pathological features are lacking. We screened and analyzed patients with newly diagnosed kidney diseases after inactivated SARS-CoV-2 vaccination in Peking University First Hospital from January 2021 to August 2021, and compared them with the reported cases in the literature. We obtained samples of blood, urine and renal biopsy tissues. Clinical and laboratory information, as well as light microscopy, immunostaining and ultrastructural observations, were described. The SARS-CoV-2 spike protein and nucleoprotein were stained using the immunofluorescence technique in the kidney biopsy samples. SARS-CoV-2 specific antibodies were tested using magnetic particle chemiluminescence immunoassay. The study group included 17 patients with a range of conditions including immune-complex-mediated kidney diseases (IgA nephropathy, membranous nephropathy and lupus nephritis), podocytopathy (minimal change disease and focal segmental glomerulosclerosis) and others (antineutrophil-cytoplasmic-antibody-associated vasculitis, anti-glomerular basement membrane nephritis, acute tubulointerstitial nephritis and thrombotic microangiopathy). Seven patients (41.18%) developed renal disease after the first dose and ten (58.82%) after the second dose. The kidney disease spectrum as well as clinicopathological features are similar across different types of SARS-CoV-2 vaccines. We found no definitive evidence of SARS-CoV-2 spike protein or nucleoprotein deposition in the kidney biopsy samples. Seropositive markers implicated abnormal immune responses in predisposed individuals. Treatment and follow-up (median = 86 days) showed that biopsy diagnosis informed treatment and prognosis in all patients. In conclusion, we observed various kidney diseases following SARS-CoV-2 vaccine administration, which show a high consistency across different types of SARS-CoV-2 vaccines. Our findings provide evidence against direct vaccine protein deposition as the major pathomechanism, but implicate abnormal immune responses in predisposed individuals. These findings expand our understanding of SARS-CoV-2 vaccine renal safety.

Act or Wait-and-See? Adversity, Agility, and Entrepreneur Wellbeing across Countries during the COVID-19 Pandemic: ET&P

How can entrepreneurs protect their wellbeing during a crisis? Does engaging agility (namely, opportunity agility and planning agility) in response to adversity help entrepreneurs safeguard their wellbeing? Activated by adversity, agility may function as a specific resilience mechanism enabling positive adaption to crisis. We studied 3162 entrepreneurs from 20 countries during the COVID-19 pandemic and found that more severe national lockdowns enhanced firm-level adversity for entrepreneurs and diminished their wellbeing. Moreover, entrepreneurs who combined opportunity agility with planning agility experienced higher wellbeing but planning agility alone lowered wellbeing. Entrepreneur agility offers a new agentic perspective to research on entrepreneur wellbeing.

Fear of COVID-19 and employee mental health in quarantine hotels: The role of self-compassion and psychological resilience at work.

The COVID-19 pandemic has had a massive and unprecedented impact on the mental health of individuals worldwide. Quarantine hotel employees not only endured enormous upheavals when providing service to quarantine guests during obligatory quarantine periods, but also experienced the high mental stress that comes with the risk of exposure and contagion of themselves, their friends, and their families. This study investigated the impact of the fear of COVID-19 on mental health problems. The moderating roles of self-compassion and psychological resilience were also examined. Data was collected from 360 employees from thirteen "Alternative State Quarantine" hotels in Thailand. The results suggested that fear of COVID-19 positively influenced mental health problems. Self-compassion and psychological resilience at work buffered the detrimental impact of fear of COVID-19 on mental health. This three-way interaction demonstrated that employees with high self-compassion and high resilience coped better. The theoretical and practical implications for hospitality managers are discussed.

Efficacy of the neutralizing antibodies after the booster dose on SARS-CoV-2 Omicron variant and a two-year longitudinal antibody study on Wild Type convalescents.

OBJECTIVES: Waning vaccine-induced immunity and emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants which may lead to immune escape, pose a major threat to the COVID-19 pandemic. Currently, enhanced efficacy of the neutralization antibodies (NAb) produced after the booster dose of vaccinations against the Omicron variant is the main focus of vaccine strategy research. In this study we have analyzed the potency of the NAbs and IgGs produced after the third vaccine dose in patients infected with Omicron variant and wild-type (WT) SARS-CoV-2. METHODS: We enrolled 75 patients with Omicron variant breakthrough infections, and 87 patients with WT infections. We recorded the clinical characteristics and vaccination information of all patients and measured the NAb and anti-S1 (spike protein) + N (nucleocapsid protein) IgG-binding antibodies against SARS-CoV-2 in serum samples of Omicron variant-infected patients at admission, and patients with WT COVID-19 infection from the time of admission and discharge, and one-year to two-years follow-ups. RESULTS: Our results demonstrated higher NAb levels, fewer clinical symptoms, and faster viral shedding in Omicron variant infected patients vaccinated with the booster dose. Hybrid immunity (natural infection plus vaccination) induces higher NAb levels than vaccine-only immunity. NAb and IgG levels decreased significantly at one-year follow-up in WT convalescents with natural infection. The NAb and IgG levels in booster-vaccinated COVID-19 patients were higher than those in two-dose-vaccinated patients. CONCLUSION: Our results suggest that booster vaccinations are required to improve the level of protective NAbs. Moreover, our data provide important evidence for vaccination strategies based on existing vaccines.

Investigation on mental health status and psychological service demands of volunteers during the epidemic

Objective: To comprehend the mental health status and its influencing factors of volunteers during the epidemic. Methods: In March 2020, through the network platform, 384 volunteers who participated in the epidemic prevention and control work in Jinshan District of Shanghai were surveyed by cluster sampling. Perceived stress scale (PSS-10), generalized anxiety disorder (GAD-7) and patient health questionnaire (PHQ-9) were used to evaluate the stress status, anxiety symptoms and depression symptoms of the subjects, and the psychological service demands of the subjects were investigated. Results: Totally 361 valid questionnaires were received with the recovery rate of 94.01%. It was found that 101 people (27.98%) had stress symptoms, 65 people (18.01%) had anxiety symptoms, and 67 people (18.56%) had depression symptoms. Among these, 61 people (16.90%) had two or more types of positive symptoms at the same time. Logistic regression analysis showed that more than 12 hours of volunteer service per week was a risk factor for stress (OR = 2.100, P < 0.05), while the familiarity with COVID-19 epidemic was a risk factor for anxiety (OR = 2.507), depression (OR = 2.674) and high-risk psychological status (OR = 2.742) (P < 0.05). People with stress, anxiety, depression and high-risk mental health status had stronger demands for mental health services (P < 0.05). Conclusions: In the early stage of the epidemic, the mental health of volunteers participating in prevention and control of epidemic in Jinshan District of Shanghai was not bad. However, it is still suggested that we should improve the construction of volunteer service system and pay attention to the physical and mental health of volunteers, establish a reasonable rest system and personal protection and social support system, emphasize the publicity and education of mental health, and provide necessary mental health services for volunteers in serious public health events.

Cultural differences in the construal of suffering and the COVID-19 pandemic

The present research examines how suffering is construed across cultures. Study 1 (N1 = 264;N2 = 745) asked participants to provide free associations for suffering. Chinese individuals generated more positive associations than did Euro-Canadians. Study 2 (N = 522) had participants create a hypothetical potion of suffering to represent what people would experience while suffering. Chinese participants added more positive ingredients and fewer negative ingredients than Euro-Canadians did. How would cultural differences in the construal of suffering matter in a real-life negative situation? Study 3 (N = 608) showed that Chinese participants generated a greater proportion of potential positive outcomes for the COVID-19 outbreak and reported more positive affect during the pandemic than did Euro-Canadians. Thus, Chinese construe suffering more positively than Euro-Canadians. These findings are consistent with previous research on cultural differences in dialectical thinking and lay theory of change and have implications for coping and resilience. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Health Behaviours among Travellers Regarding Risk Compensation Following COVID-19 Vaccination in Taizhou, China.

Background: During the COVID-19 pandemic, public transport was restricted in many countries because of the transmission risk. According to the risk compensation theory, travellers post-COVID-19 vaccination may encounter higher risks; however, no real-world studies provide such evidence. Therefore, we conducted a survey to assess whether risk compensation would occur among travellers' health-related behaviours after COVID-19 vaccination, potentially aggravating the transmission of the virus. Materials and Methods: A self-administered online survey was designed and distributed over WeChat to identify the difference in health behaviours before and after COVID-19 vaccination among travellers at a train station in Taizhou, China, from 13 February to 26 April 2022. Results: A total of 602 individuals completed the questionnaire. The results revealed no statistical difference between the health behaviours reported by the vaccinated and unvaccinated groups. Participants who received the first dose of the vaccine earlier showed no statistical difference in harmful health behaviours (hand washing frequency decreased by 4.1% (P=0.145) and the duration of public transport travel increased by 3.4% (P=0.437)), but showed better protective health behaviours (mask-wearing duration increased by 24.7% (P=0.014)). Compared to those vaccinated less than three times, participants vaccinated against COVID-19 three times showed no statistical differences in harmful health behaviours mask-wearing duration decreased by 7.0% (P=0.927), their hand washing frequency decreased by 4.8% (P=0.905), and the duration of public transport travel increased by 2.5% (P=0.287). After vaccination, when compared to themselves before vaccination, participants exhibited better health behaviours (increased hand washing frequency and mask-wearing duration, and decreased duration of public transport travel) to some extent. Conclusion: In conclusion, this study found no evidence of risk compensation among travellers. After being vaccinated, health behaviours partly improved among travellers.

Therapeutic potential of salicylamide derivatives for combating viral infections.

Since time immemorial human beings have constantly been fighting against viral infections. The ongoing and devastating coronavirus disease 2019 pandemic represents one of the most severe and most significant public health emergencies in human history, highlighting an urgent need to develop broad-spectrum antiviral agents. Salicylamide (2-hydroxybenzamide) derivatives, represented by niclosamide and nitazoxanide, inhibit the replication of a broad range of RNA and DNA viruses such as flavivirus, influenza A virus, and coronavirus. Moreover, nitazoxanide was effective in clinical trials against different viral infections including diarrhea caused by rotavirus and norovirus, uncomplicated influenza A and B, hepatitis B, and hepatitis C. In this review, we summarize the broad antiviral activities of salicylamide derivatives, the clinical progress, and the potential targets or mechanisms against different viral infections and highlight their therapeutic potential in combating the circulating and emerging viral infections in the future.

Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura: a case report and review of the literature.

BACKGROUND: Immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura are both causes of thrombocytopenia. Recognizing thrombotic thrombocytopenic purpura is crucial for subsequent treatment and prognosis. In clinical practice, corticosteroids and rituximab can be used to treat both immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura; plasma exchange therapy is the first-line treatment in thrombotic thrombocytopenic purpura, while corticosteroids are strongly recommended as first-line treatment in immune thrombocytopenic purpura. The differential diagnosis of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is essential in clinical practice. However, case reports have suggested that immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura can occur concurrently. CASE PRESENTATION: We report the case of a 32-year-old Asian female without previous disease who presented with pancytopenia, concurrent with immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura. The morphology of the megakaryocytes in the bone marrow indicated immune-mediated thrombocytopenia. The patient received glucocorticoid treatment, and her platelet count increased; however, schistocytes remained high during the course of the therapy. Further investigations revealed ADAMTS13 activity deficiency and positive ADAMTS13 antibodies. The high titer of antinuclear antibody and positive anti-U1-ribonucleoprotein/Smith antibody indicated a potential autoimmune disease. However, the patient did not fulfill the current criteria for systemic lupus erythematosus or mixed connective tissue disease. The patient responded well to plasma exchange therapy, and her platelet count remained normal on further follow-up. CONCLUSIONS: Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is rare, but clinicians should be aware of this entity to ensure prompt medical intervention. Most of the reported cases involve young women. Human immunodeficiency virus infection, pregnancy, and autoimmune disease are the most common underlying conditions.

Proteomics Investigation of Diverse Serological Patterns in COVID-19.

Serum antibodies IgM and IgG are elevated during Coronavirus Disease 2019 (COVID-19) to defend against viral attacks. Atypical results such as negative and abnormally high antibody expression were frequently observed whereas the underlying molecular mechanisms are elusive. In our cohort of 144 COVID-19 patients, 3.5% were both IgM and IgG negative, whereas 29.2% remained only IgM negative. The remaining patients exhibited positive IgM and IgG expression, with 9.3% of them exhibiting over 20-fold higher titers of IgM than the others at their plateau. IgG titers in all of them were significantly boosted after vaccination in the second year. To investigate the underlying molecular mechanisms, we classed the patients into four groups with diverse serological patterns and analyzed their 2-year clinical indicators. Additionally, we collected 111 serum samples for TMTpro-based longitudinal proteomic profiling and characterized 1494 proteins in total. We found that the continuously negative IgM and IgG expression during COVID-19 were associated with mild inflammatory reactions and high T cell responses. Low levels of serum IgD, inferior complement 1 activation of complement cascades, and insufficient cellular immune responses might collectively lead to compensatory serological responses, causing overexpression of IgM. Serum CD163 was positively correlated with antibody titers during seroconversion. This study suggests that patients with negative serology still developed cellular immunity for viral defense and that high titers of IgM might not be favorable to COVID-19 recovery.