Novel evidence of Thymosin α1 immunomodulatory properties in SARS-CoV-2 infection: Effect on innate inflammatory response in a peripheral blood mononuclear cell-based in vitro model.

The peculiar property of Thymosin alpha 1 (Tα1) to act as master regulator of immune homeostasis has been successfully defined in different physiological and pathological contexts ranging from cancer to infection. Interestingly, recent papers also demonstrated its mitigating effect on the "cytokine storm" as well as on the T-cell exhaustion/activation in SARS-CoV-2 infected individuals. Nevertheless, in spite of the increasing knowledge on Tα1-induced effects on T cell response confirming the distinctive features of this multifaceted peptide, little is known on its effects on innate immunity during SARS-CoV-2 infection. Here, we interrogated peripheral blood mononuclear cell (PBMC) cultures stimulated with SARS-CoV-2 to disclose Tα1 properties on the main cell players of early response to infection, namely monocytes and myeloid dendritic cells (mDC). Moving from ex vivo data showing an enhancement in the frequency of inflammatory monocytes and activated mDC in COVID-19 patients, a PBMC-based experimental setting reproduced in vitro a similar profile with an increased percentage of CD16+ inflammatory monocytes and mDC expressing CD86 and HLA-DR activation markers in response to SARS-CoV-2 stimulation. Interestingly, the treatment of SARS-CoV-2-stimulated PBMC with Tα1 dampened the inflammatory/activation status of both monocytes and mDC by reducing the release of pro-inflammatory mediators, including TNF-α, IL-6 and IL-8, while promoting the production of the anti-inflammatory cytokine IL-10. This study further clarifies the working hypothesis on Tα1 mitigating action on COVID-19 inflammatory condition. Moreover, these evidence shed light on inflammatory pathways and cell types involved in acute SARS-CoV-2 infection and likely targetable by newly immune-regulating therapeutic approaches.

A pilot trial of Thymalfasin (Ta1) to prevent covid-19 infection and morbidities in renal dialysis patients: Preliminary report.

PURPOSE: Patients with end-stage renal disease (ESRD) on hemodialysis (HD) are considered particularly susceptible to infection with SARS-CoV2 on the basis of the immunodeficiency associated with advanced age, comorbidity burden, medication use, and need for frequent visits to dialysis clinics. In prior studies, thymalfasin (thymosin alpha 1, Ta1) has been shown to enhance antibody response to influenza vaccine and reduce influenza infection in geriatric populations, including hemodialysis patients, when used as an adjunct to influenza vaccine. Early in the COVID-19 pandemic we speculated that administration of Ta1 to HD patients would result in reduced rate and severity of COVID-19 infection. We also hypothesized that HD patients treated with Ta1 who did become infected with COVID-19 would have a milder course of infection in terms of hospitalization rates, requirement for and length of ICU stays, requirement for mechanical ventilation, and survival. Further, we proposed that patients who avoided COVID-19 infection during the study would have decreased non-COVID-19 infections and hospitalizations compared to controls. PROCEDURES: The study launched in January 2021 and, as of July 1, 2022, 254 ESRD/ HD patients from five dialysis centers in Kansas City, MO have been screened. Of these, 194 patients have been randomized 1:1 to either Group A (1.6 mg Ta1 given subcutaneously twice weekly for 8 weeks), or Group B (control group not receiving Ta1). After the 8-week treatment period, subjects were followed for an additional 4 months and monitored for safety and efficacy. A data safely monitoring board reviewed all reported adverse effects and commented on study progress. RESULTS: To date, only 3 deaths have occurred in subjects treated with Ta1 (Group A), compared to 7 in the control (Group B). There have been 12 COVID-19 related serious adverse effects (SAEs; 5 in Group A, and 7 in Group B). The majority of patients have received a COVID-19 vaccine (91 patients in group A, and 76 patients in Group B) at various times throughout the study. Nearing completion of the study, blood samples have been collected and antibody responses to COVID-19 will be analyzed along with safety and efficacy endpoints when all subjects have completed the study.

Thymosin alpha 1 restores the immune homeostasis in lymphocytes during Post-Acute sequelae of SARS-CoV-2 infection.

The complex alterations of the immune system and the immune-mediated multiorgan injury plays a key role in host response to SARS-CoV-2 infection and in the pathogenesis of COVID-19, being also associated with adverse outcomes. Thymosin alpha 1 (Tα1) is one of the molecules used in the treatment of COVID-19, as it is known to restore the homeostasis of the immune system during infections and cancer. The use of Tα1 in COVID-19 patients had been widely used in China and in COVID-19 patients, it has been shown to decrease hospitalization rate, especially in those with greater disease severity, and reduce mortality by restoring lymphocytopenia and more specifically, depleted T cells. Persistent dysregulation with depletion of naive B and T cell subpopulations and expansion of memory T cells suggest a chronic stimulation of the immune response in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Our data obtained from an ex vivo study, showed that in PASC individuals with a chronically altered immune response, Tα1 improve the restoration of an appropriate response, most evident in those with more severe illness and who need respiratory support during acute phase, and in those with specific systemic and psychiatric symptoms of PASC, confirming Tα1 treatment being more effective in compromised patients. The results obtained, along with promising reports on recent trials on Tα1 administration in patients with COVID-19, offer new insights into intervention also for those patients with long-lasting inflammation with post-infectious symptoms, some of which have a delayed onset.

Thymosin alpha 1 - Reimagine its broader applications in the immuno-oncology era.

Thymosin alpha 1 (Tα1) is a highly conserved 28 amino-acid peptide naturally occurring in the thymus and plays critical roles in T cell maturity and differentiation. Its synthetic form, thymalfasin, has been approved by various regulatory agencies in the treatment of hepatitis B viral infection and as an enhancer of vaccine response in immune-compromised populations. In China, it has also widely utilized in patients with cancer and severe infections, as well as the emergency use during (Severe Acute Respiratory Syndrome)SARS and COVID-19 pandemic as an immune-regulator. Recent studies showed that Tα1 could significantly improve overall survival (OS) in patients with surgically resectable non-small cell lung cancer (NSCLC) and liver cancers in the adjuvant setting. For patients with locally advanced, unresectable NSCLC, Tα1 could significantly reduce chemoradiation-induced lymphopenia, pneumonia, and trending improvement of OS. Preclinical evidence are emerging to demonstrate that Tα1 may augment efficacy of cancer chemotherapy by reversing efferocytosis-induced M2 polarization of macrophages via activation of a TLR7/SHIP1 axis and enhancing anti-tumor immunity by turning "cold-tumors" to "hot-tumors"; a protective role in reducing colitis caused by immune check-point inhibitors (ICIs). Potential enhancement of ICIs' clinical efficacies has also been indicated. ICIs have transformed ways treating patients with cancer but limitations such as relatively low response rates and certain safety issues remains. Given the roles of Tα1 in regulating cellular immunities and exceptional safety profiles demonstrated in decades clinical uses, we believe that it is plausible to explore implications of Tα1 the immune-oncology setting by combining with ICI-based therapeutic strategies. Background Activities of Tα1. Tα1 is a biological response modifier which activates various cells in the immune system [1-3]. Tα1 is therefore expected to have clinical benefits in disorders where immune responses are impaired or ineffective. These disorders include acute and chronic infections, cancers, and vaccine non-responsiveness. In severe sepsis, for example, sepsis-induced immunosuppression is increasingly recognized as the overriding immune dysfunction in these vulnerable patients [4] and there is now agreement that many patients with severe sepsis survive the first critical hours of the syndrome but eventually die later due to patients' immunosuppression which make the system difficulty to fight the primary bacterial infection, decreased resistance to secondary nosocomial infections, and reactivation of viral infections [5]. Tα1 has been shown to restore immune functions and help to reduce mortality in patients with severe sepsis.

COVID-19 and beyond: Reassessing the role of thymosin alpha1 in lung infections.

The recent COVID-19 pandemic has catalyzed the attention of the scientific community to the long-standing issue of lower respiratory tract infections. The myriad of airborne bacterial, viral and fungal agents to which humans are constantly exposed represents a constant threat to susceptible individuals and bears the potential to reach a catastrophic scale when the ease of inter-individual transmission couples with a severe pathogenicity. While we might be past the threat of COVID-19, the risk of future outbreaks of respiratory infections is tangible and argues for a comprehensive assessment of the pathogenic mechanisms shared by airborne pathogens. On this regard, it is clear that the immune system play a major role in dictating the clinical course of the infection. A balanced immune response is required not only to disarm the pathogens, but also to prevent collateral tissue damage, thus moving at the interface between resistance to infection and tolerance. Thymosin alpha1 (Tα1), an endogenous thymic peptide, is increasingly being recognized for its ability to work as an immunoregulatory molecule able to balance a derailed immune response, working as immune stimulatory or immune suppressive in a context-dependent manner. In this review, we will take advantage from the recent work on the COVID-19 pandemic to reassess the role of Tα1 as a potential therapeutic molecule in lung infections caused by either defective or exaggerated immune responses. The elucidation of the immune regulatory mechanisms of Tα1 might open a new window of opportunity for the clinical translation of this enigmatic molecule and a potential new weapon in our arsenal against lung infections.

Thymosin alpha1 use in adult COVID-19 patients: A systematic review and meta-analysis on clinical outcomes.

OBJECTIVE: Thymosin alpha1 (Ta1) is widely used to treat patients with coronavirus disease 2019 (COVID-19), however, its effect remains unclear. This systematic review and meta-analysis aimed to evaluate the effect of Ta1 as a COVID-19 therapy. METHODS: PubMed, EMBASE, the Cochrane library, Web of Science, and the reference lists of relevant articles were searched to identify eligible studies. Assessment of heterogeneity was done using the I-squared (I2) test and random/fixed effect analysis was done to determine the risk ratio (RR). We polled the data related to mortality mainly by using Review Manager 5.4. Predefined subgroup analyses and sensitivity analyses were also performed. RESULTS: A total of 9 studies were included, on a total of 5352 (Ta1 = 1152, control = 4200) patient outcomes. Meta-analysis results indicated that Ta1 therapy had no statistically significant effect on mortality [RR 1.03 (0.60, 1.75), p = 0.92, I2 = 90 %]. Subgroup analyses demonstrated that the beneficial effect in mortality was associated with mean age＞60 years in the Tα1 group [RR 0.68 (0.58, 0.78), p < 0.0000.1, I2 = 0 %], the proportion of female ≤ 40 % in the Tα1 group [RR 0.67 (0.58, 0.77), p < 0.0000.1, I2 = 0 %], and severe/critical COVID-19 patients [RR 0.66 (0.57, 0.76), p < 0.0000.1, I2 = 0 %]. Sensitivity analysis further demonstrated the results to be robust. CONCLUSIONS: The results of this meta-analysis do not support the use of Ta1 in hospitalized adult COVID-19 patients.

[Thymosin alpha 1 for the adjuvant treatment of coronavirus disease 2019: a retrospective cohort study].

OBJECTIVE: To evaluate the effect of thymosin alpha 1 on the prognosis of patients with coronavirus disease 2019 (COVID-19). METHODS: A retrospective cohort study was performed to collect clinical data of 95 patients treated by Shanghai Aid Medical Team in Wuhan Third Hospital during January 31, 2020 and March 4, 2020, who were confirmed COVID-19. They were divided into two groups according to whether they were treated with thymosin alpha 1 after admission. The 28-day mortality (primary outcome), and 28-ventilator-free-day, lymphocyte count (LYM) level, C-reactive protein (CRP) level (secondary outcomes) were compared between two groups. Survival analysis was performed using the Kaplan-Meier curve. The effect of thymosin alpha 1 on 28-day survival was evaluated with Cox regression model. RESULTS: Among the 95 patients, there were 31 cases in thymosin group and 64 cases in non-thymosin group; 29 patients died 28 days after admission, including 11 cases (35.5%) in thymosin group and 18 cases (28.1%) in non-thymosin group. Kaplan-Meier survival curve showed that thymosin alpha 1 could improve the 28-day survival of patients with COVID-19, but the univariate Cox model analysis showed that the difference was not statistically significant [hazard ratio (HR) = 0.48, 95% confidence interval (95%CI) was 0.20-1.14, P = 0.098]; multivariate Cox model analysis showed that thymosin alpha 1 was the factor to improve the 28-day mortality (HR = 0.15, 95%CI was 0.04-0.55, P = 0.004), old age (HR = 1.10, 95%CI was 1.05-1.15, P < 0.001), accompanied by chronic renal dysfunction (HR = 42.35, 95%CI was 2.77-648.64, P = 0.007), decrease of LYM at admission (HR = 0.15, 95%CI was 0.04-0.60, P = 0.007) and the use of methylprednisolone (HR = 4.59, 95%CI was 1.26-16.67, P = 0.021) were also risk factors for the increase of 28-day mortality. The use of immunoglobulin and antiviral drugs abidol and ganciclovir did not affect the 28-day mortality. After adjustment for age, gender, LYM and other factors, weighted multivariate Cox analysis model showed thymosin alpha 1 could significantly improve the 28-day survival of COVID-19 patients (HR = 0.45, 95%CI was 0.25-0.84, P = 0.012). In terms of secondary outcomes, no statistical difference (all P > 0.05) was found between two groups in days without ventilator at 28 days after admission (days: 17.97±13.56 vs. 20.09±12.67) and the increase of LYM at 7 days after admission [×109/L: -0.07 (-0.23, 0.43) vs. 0.12 (-0.54, 0.41)]. But the decrease of CRP at 7 days after admission in thymosin alpha group was significantly greater than that in non-thymosin group [mg/L: 39.99 (8.44, 82.22) vs. 0.53 (-7.78, 22.93), P < 0.05]. CONCLUSION: Thymosin alpha 1 may improve 28-day mortality and inflammation state in COVID-19 patients.

Thymosin Alpha-1 Has no Beneficial Effect on Restoring CD4+ and CD8+ T Lymphocyte Counts in COVID-19 Patients.

Dysregulation of immune response was observed in COVID-19 patients. Thymosin alpha 1 (Tα1) is used in the management of COVID-19, because it is known to restore the homeostasis of the immune system during infections and cancers. We aim to observe the longitudinal changes in T lymphocyte subsets and to evaluate the efficacy of Tα1 for COVID-19. A retrospective study was conducted in 275 COVID-19 patients admitted to Shanghai public health clinical center. The clinical and laboratory characteristics between patients with different T lymphocyte phenotypes and those who were and were not treated with Tα1 were compared. Among the 275 patients, 137 (49.8%) were males, and the median age was 51 years [interquartile range (IQR): 37-64]. A total of 126 patients received Tα1 therapy and 149 patients did not. There were 158 (57.5%) patients with normal baseline CD4 counts (median:631/µL, IQR: 501~762) and 117 patients (42.5%) with decreased baseline CD4 counts (median:271/µL, IQR: 201~335). In those with decreased baseline CD4 counts, more patients were older (p<0.001), presented as critically ill (p=0.032) and had hypertension (p=0.008) compared with those with normal CD4 counts. There was no statistical difference in the duration of virus shedding in the upper respiratory tract between the two groups (p=0.214). In both the normal (14 vs 11, p=0.028) and the decreased baseline CD4 counts group (15 vs 11, p=0.008), duration of virus clearance in the patients with Tα1 therapy was significantly longer than that in those without Tα1 therapy. There was no significant difference in the increase of CD4+ (286 vs 326, p=0.851) and CD8+ T cell (154 vs 170, p=0.842) counts in the recovery period between the two groups with or without Tα1 therapy. Multivariate linear regression analysis showed that severity of illness (p<0.001) and Tα1 therapy (p=0.001) were associated with virus clearance. In conclusion, reduction of CD4+ T and CD8+ T cell counts were observed in COVID-19 patients. Tα1 may have no benefit on restoring CD4+ and CD8+ T cell counts or on the virus clearance. The use of Tα1 for COVID-19 need to be more fully investigated.

Dysfunctional Inflammation in Cystic Fibrosis Airways: From Mechanisms to Novel Therapeutic Approaches.

Cystic fibrosis (CF) is an inherited disorder caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an ATP-gated chloride channel expressed on the apical surface of airway epithelial cells. CFTR absence/dysfunction results in defective ion transport and subsequent airway surface liquid dehydration that severely compromise the airway microenvironment. Noxious agents and pathogens are entrapped inside the abnormally thick mucus layer and establish a highly inflammatory environment, ultimately leading to lung damage. Since chronic airway inflammation plays a crucial role in CF pathophysiology, several studies have investigated the mechanisms responsible for the altered inflammatory/immune response that, in turn, exacerbates the epithelial dysfunction and infection susceptibility in CF patients. In this review, we address the evidence for a critical role of dysfunctional inflammation in lung damage in CF and discuss current therapeutic approaches targeting this condition, as well as potential new treatments that have been developed recently. Traditional therapeutic strategies have shown several limitations and limited clinical benefits. Therefore, many efforts have been made to develop alternative treatments and novel therapeutic approaches, and recent findings have identified new molecules as potential anti-inflammatory agents that may exert beneficial effects in CF patients. Furthermore, the potential anti-inflammatory properties of CFTR modulators, a class of drugs that directly target the molecular defect of CF, also will be critically reviewed. Finally, we also will discuss the possible impact of SARS-CoV-2 infection on CF patients, with a major focus on the consequences that the viral infection could have on the persistent inflammation in these patients.

The effect of thymosin α1 on mortality of critical COVID-19 patients: A multicenter retrospective study.

BACKGROUND: Thymosin α1 therapy was commonly used in patients with coronavirus disease 2019 (COVID-19), while its impact on outcomes and which patients could benefit from thymosin α1 therapy were uncertain. STUDY DESIGN AND METHODS: Patients with COVID-19 from 19 designated hospitals between January 1 to February 29, 2020 were included, and the main exposure of interest was administration of thymosin α1. The primary outcome was 28-day mortality. Propensity score matching (PSM) was used to account for baseline confounders, cluster analysis and Cox proportional hazard model was used to account for subgroup analysis. RESULTS: A total of 771 patients were included, and 327/771 (42.4%) patients received thymosin α1 therapy. The 28-day mortality in thymosin group was significantly lower than that in control group (41.3% vs. 60.6%, p < 0.001). After PSM 522 patients were included in analysis and the 28-day mortality in thymosin α1 group and control group were 51.0% and 52.9% respectively, with no significant difference. In subgroup analyses, the association between thymosin α1 therapy and 28-day mortality appeared to be stronger among male patients (HR 0.673, 95% CI 0.454-0.998; p = 0.049). There were no benefits of thymosin α1 in 28-day mortality in other subgroups. There were two phenotypes after cluster analysis, but no benefits of thymosin α1 were shown in phenotype 1 (HR 0.823 95% CI 0.581-1.166; p = 0.273) and phenotype 2 (HR 1.148 95% CI 0.710-1.895; p = 0.442). CONCLUSION: There was no association between use of thymosin α1 and decreased mortality in critically ill COVID-19 patients. Subgroups analysis and phenotype analysis also showed no differences on mortality after thymosin α1 therapy.

The right immune-modulation at the right time: thymosin α1 for prevention of severe COVID-19 in cancer patients.

We presented the rationale for the use of thymosin α1 as prophylaxis of severe COVID-19 in cancer patients undergoing active treatment, constituting the background for the PROTHYMOS study, a prospective, multicenter, open-label, Phase II randomized study, currently in its start-up phase (Eudract no. 2020-006020-13). We aim to offer new hope for this incurable disease, especially to frail patient population, such as patients with cancer. The hypothesis of an effective prophylactic approach to COVID-19 would have immediate clinical relevance, especially given the lack of curative approaches. Moreover, in the 'COVID-19 vaccine race era' both clinical and biological results coming from the PROTHYMOS trials could even support the rationale for future combinatorial approaches, trying to rise vaccine efficacy in frail individuals.

Gender-associated difference following COVID-19 virus infection: Implications for thymosin alpha-1 therapy.

Gender influences clinical presentations, duration and severity of symptoms, and therapy outcome in coronavirus disease 2019 (COVID-19) infection. Whether the immune response to Tα1 treatment for SARS-CoV-2 differs between the sexes, and whether this difference explains the male susceptibility to COVID-19, is unclear. This study aimed to investigate the efficiency and safety of Tα1 treatment and provide a basis for practically identifying gender differences characteristics and features of COVID-19. One hundred twenty-seven patients had COVID-19 symptoms and tested COVID19-positive (female 42.52%) in Wuhan union hospital were enrolled for medication. They were randomly divided into groups Control and Tα1 intervention. Seventy-eight patients received a subcutaneous injection of 1.6 mg Tα1, based on supportive treatment for 15 days. The control group included untreated 49 COVID19 patients closely matched for gender and age and received regular supportive treatment. In this retrospective analysis, we found that COVID-19-infected males reported more symptoms than COVID-19-infected females. A high degree of gender differences-related variability was observed in CRP and PCT levels and the cell counts of many lymphocyte subpopulations in the COVID-19 patients after Tα1 intervention. Levels of CRP and IL-6 were higher in Tα1-treated male group than Tα1-treated female group, while the level of PCT was significantly lower in Tα1-treated male group. Gender differences may be a factor in sustaining COVID-19 immunity responded to Tα1, male and female show statistically significant differences in relevance to cytokine production associated with the development of a more significant number of symptoms. This leaves the question of identifying gender-specific risk factors to explain these differences.

Thymosin α1 therapy in critically ill patients with COVID-19: A multicenter retrospective cohort study.

BACKGROUND: COVID-19 characterized by refractory hypoxemia increases patient mortality because of immunosuppression effects. This study aimed to evaluate the efficacy of immunomodulatory with thymosin α1 for critical COVID-19 patients. METHODS: This multicenter retrospective cohort study was performed in 8 government-designated treatment centers for COVID-19 patients in China from Dec. 2019 to Mar. 2020. Thymosin α1 was administrated with 1.6 mg qd or q12 h for >5 days. The primary outcomes were the 28-day and 60-day mortality, the secondary outcomes were hospital length of stay and the total duration of the disease. Subgroup analysis was carried out according to clinical classification. RESULTS: Of the 334 enrolled COVID-19 patients, 42 (12.6%) died within 28 days, and 55 (16.5%) died within 60 days of hospitalization. There was a significant difference in the 28-day mortality between the thymosin α1 and non-thymosin α1-treated groups in adjusted model (P = 0.016), without obvious differences in the 60-day mortality and survival time in the overall cohort (P > 0.05). In the subgroup analysis, it was found that thymosin α1 therapy significantly reduced 28-day mortality (Hazards Ratios HR, 0.11, 95% confidence interval CI 0.02-0.63, P=0.013) via improvement of Pa02/FiO2 (P = 0.036) and prolonged the hospital length of stay (P = 0.024) as well as the total duration of the disease (P=0.001) in the critical type patients, especially those aged over 64 years, with white blood cell >6.8×109/L, neutrophil >5.3×109/L, lymphocyte < 0.73 × 109/L, PaO2/FiO2 < 196, SOFA > 3, and acute physiology and chronic health evaluation (APACHE) II > 7. CONCLUSION: These results suggest that treatment with thymosin α1 can markedly decrease 28-day mortality and attenuate acute lung injury in critical type COVID-19 patients.

A Convalescent of COVID-19 with RT-PCR Test Continues Positive in Stool.

BACKGROUND: Coronavirus disease (COVID-19) has affected more than 100 countries worldwide and the discharge criteria of patients with COVID-19 vary across different countries. In China, patients with two negative respiratory viral RNA tests taken at least one day apart can be discharged with no further quarantine required. Currently, PCR testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in fecal sample is not routinely performed. METHODS: We present a patient with COVID-19, whose respiratory swabs became negative but fecal sample remained positive for SARS-CoV-2 RNA. RESULTS: Stool sample collected on 27th of February was still positive for SARS-CoV-2 RNA, 24 days after the first negative respiratory swab. CONCLUSIONS: Based on the experience from the 2003 SARS epidemic, we recommend that fecal RNA testing of SARS-CoV-2 should be incorporated into the discharge criteria to minimize the risk of transmission from the gastrointestinal tract.

Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells: A case report.

RATIONALE: The COVID-19 cases increased very fast in January and February 2020. The mortality among critically ill patients, especially the elder ones, is relatively high. Considering many patients died of severe inflammation response, it is urgent to develop effective therapeutic strategies for these patients. The human umbilical cord mesenchymal stem cells (hUCMSCs) have shown good capabilities to modulate the immune response and repair the injured tissue. Therefore, investigating the potential of hUCMSCs to the treatment of COVID-19 critically ill patients is necessary. PATIENT CONCERNS: A 65-year-old woman felt fatigued and had a fever with body temperature of 38.2C, coughed up white foaming sputum. After 1 day, she had chest tightness with SPO2 of 81%, and blood pressure of 160/91 mm Hg. DIAGNOSE: According to the guideline for the diagnosis and treatment of 2019 novel coronavirus infected pneumonia (Trial 4th Edition), COVID-19 was diagnosed, based on the real-time RT-PCR test of SARS-CoV-2. INTERVENTIONS: After regular treatment for 12 days, the inflammation symptom of the patient was still very severe and the potential side effects of corticosteroid were observed. Then, allogenic hUCMSCs were given 3 times (5 × 10 cells each time) with a 3-day interval, together with thymosin α1 and antibiotics daily injection. OUTCOMES: After these treatments, most of the laboratory indexes and CT images showed remission of the inflammation symptom. The patient was subsequently transferred out of ICU, and the throat swabs test reported negative 4 days later. LESSONS: These results indicated the clinical outcome and good tolerance of allogenic hUCMSCs transfer.

The severe COVID-19: A sepsis induced by viral infection? And its immunomodulatory therapy.

COVID-19 is known for its magical infectivity, fast transmission and high death toll based on the large number of infected people. From the perspective of the clinical manifestation, autopsy examination and pathophysiology, the essence of COVID-19 should be viewed as a sepsis induced by viral infection, and has the essential characteristics as sepsis induced by other pathogens. Therefore, in addition to etiological and supportive treatment, immunomodulatory therapy is also appropriate to severe COVID-19. Although there is still a lack of consensus on immunotherapy for sepsis so far, relatively rich experiences have been accumulated in the past decades, which will help us in the treatment of severe COVID-19. This article will elaborate immunotherapy of sepsis, though it may not be consistent.