The SARS-CoV-2 papain-like protease suppresses type I interferon responses by deubiquitinating STING.

The SARS-CoV-2 papain-like protease (PLpro), which has deubiquitinating activity, suppresses the type I interferon (IFN-I) antiviral response. We investigated the mechanism by which PLpro antagonizes cellular antiviral responses. In HEK392T cells, PLpro removed K63-linked polyubiquitin chains from Lys289 of the stimulator of interferon genes (STING). PLpro-mediated deubiquitination of STING disrupted the STING-IKKε-IRF3 complex that induces the production of IFN-ß and IFN-stimulated cytokines and chemokines. In human airway cells infected with SARS-CoV-2, the combined treatment with the STING agonist diABZi and the PLpro inhibitor GRL0617 resulted in the synergistic inhibition of SARS-CoV-2 replication and increased IFN-I responses. The PLpros of seven human coronaviruses (SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-229E, HCoV-HKU1, HCoV-OC43, and HCoV-NL63) and four SARS-CoV-2 variants of concern (α, ß, γ, and δ) all bound to STING and suppressed STING-stimulated IFN-I responses in HEK293T cells. These findings reveal how SARS-CoV-2 PLpro inhibits IFN-I signaling through STING deubiquitination and a general mechanism used by seven human coronaviral PLpros to dysregulate STING and to facilitate viral innate immune evasion. We also identified simultaneous pharmacological STING activation and PLpro inhibition as a potentially effective strategy for antiviral therapy against SARS-CoV-2.

The substrate selectivity of papain-like proteases from human-infecting coronaviruses correlates with innate immune suppression.

Coronaviruses that can infect humans can cause either common colds (HCoV-NL63, HCoV-229E, HCoV-HKU1, and HCoV-OC43) or severe respiratory symptoms (SARS-CoV-2, SARS-CoV, and MERS-CoV). The papain-like proteases (PLPs) of SARS-CoV, SARS-CoV-2, MERS-CoV, and HCoV-NL63 function in viral innate immune evasion and have deubiquitinating (DUB) and deISGylating activities. We identified the PLPs of HCoV-229E, HCoV-HKU1, and HCoV-OC43 and found that their enzymatic properties correlated with their ability to suppress innate immune responses. A conserved noncatalytic aspartic acid residue was critical for both DUB and deISGylating activities, but the PLPs had differing ubiquitin (Ub) chain cleavage selectivities and binding affinities for Ub, K48-linked diUb, and interferon-stimulated gene 15 (ISG15) substrates. The crystal structure of HKU1-PLP2 in complex with Ub revealed binding interfaces that accounted for the unusually high binding affinity between this PLP and Ub. In cellular assays, the PLPs from the severe disease-causing coronaviruses strongly suppressed innate immune IFN-I and NF-κB signaling and stimulated autophagy, whereas the PLPs from the mild disease-causing coronaviruses generally showed weaker effects on immune suppression and autophagy induction. In addition, a PLP from a SARS-CoV-2 variant of concern showed increased suppression of innate immune signaling pathways. Overall, these results demonstrated that the DUB and deISGylating activities and substrate selectivities of these PLPs differentially contribute to viral innate immune evasion and may affect viral pathogenicity.

The photolytic behavior of COVID-19 antivirals ribavirin in natural waters and the increased environmental risk

Increasing drug residues in aquatic environments have been caused by the abuse of antivirals since the global spread of the COVID-19 epidemic, whereas research on the photolytic mechanism, pathways and toxicity of these drugs is limited. The concentration of COVID-19 antivirals ribavirin in rivers has been reported to increase after the epidemic. Its photolytic behavior and environmental risk in actual waters such as wastewater treatment plant (WWTP) effluent, river water and lake water were first investigated in this study. Direct photolysis of ribavirin in these media was limited, but indirect photolysis was promoted in WWTP effluent and lake water by dissolved organic matter and NO3−. Identification of photolytic intermediates suggested that ribavirin was photolyzed mainly via C−N bond cleavage, splitting of the furan ring and oxidation of the hydroxyl group. Notably, the acute toxicity was increased after ribavirin photolysis owing to the higher toxicity of most of the products. Additionally, the overall toxicity was greater when ARB photolysis in WWTP effluent and lake water. These findings emphasize the necessity to concern about the toxicity of ribavirin transformation in natural waters, as well as to limit its usage and discharge. Graphical

The photolytic behavior of COVID-19 antivirals ribavirin in natural waters and the increased environmental risk.

Increasing drug residues in aquatic environments have been caused by the abuse of antivirals since the global spread of the COVID-19 epidemic, whereas research on the photolytic mechanism, pathways and toxicity of these drugs is limited. The concentration of COVID-19 antivirals ribavirin in rivers has been reported to increase after the epidemic. Its photolytic behavior and environmental risk in actual waters such as wastewater treatment plant (WWTP) effluent, river water and lake water were first investigated in this study. Direct photolysis of ribavirin in these media was limited, but indirect photolysis was promoted in WWTP effluent and lake water by dissolved organic matter and NO3-. Identification of photolytic intermediates suggested that ribavirin was photolyzed mainly via C-N bond cleavage, splitting of the furan ring and oxidation of the hydroxyl group. Notably, the acute toxicity was increased after ribavirin photolysis owing to the higher toxicity of most of the products. Additionally, the overall toxicity was greater when ARB photolysis in WWTP effluent and lake water. These findings emphasize the necessity to concern about the toxicity of ribavirin transformation in natural waters, as well as to limit its usage and discharge.

Atrial Fibrillation (AFIB) in the ICU: Incidence, Risk Factors, and Outcomes: The International AFIB-ICU Cohort Study.

OBJECTIVES: To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF. DESIGN: Multicenter, prospective, inception cohort study. SETTING: Forty-four ICUs in 12 countries in four geographical regions. SUBJECTS: Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8-17.6), of which newly developed AF was 13.3% (11.5-15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16-23), magnesium 16% (13-20), potassium 15% (12-19), amiodarone 51% (47-55), beta-1 selective blockers 34% (30-38), calcium channel blockers 4% (2-6), digoxin 16% (12-19), and direct current cardioversion in 4% (2-6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95-1.99). CONCLUSIONS: In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.

Impact of Time-To-Surgery on the Prognosis of Patients with T1 Renal Cell Carcinoma: Implications for the COVID-19 Pandemic.

Background: During the COVID-19 pandemic, elective surgery has to undergo longer wait times, including nephrectomy for T1 renal cell carcinoma (RCC). This study aimed to investigate the time-to-surgery (TTS) of Chinese T1 RCC patients and its influencing factors, and to illustrate the impact of TTS on the prognosis of T1 RCC. Methods: We retrospectively enrolled 762 Chinese patients with pathological T1 RCC that underwent nephrectomy. To discover the impact of TTS on survival outcomes, we explored the possible delay intervals by week using the Kaplan-Meier method and Log-rank test. Cox proportional hazard models with inverse probability-treatment weighting (IPTW) were used to assess the association between TTS and disease-free survival (DFS) and overall survival (OS). Results: The median TTS of T1 RCC patients was 15 days. The Charlson comorbidity index, the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score, and the maximal tumor diameter on presentation were independent influencing factors for TTS. The cut-off point of TTS was selected as 5 weeks according to the Log-rank analysis. For T1a RCC, patients with TTS > 5 weeks had similar DFS (HR = 2.39; 95% CI, 0.82−6.94; p = 0.109) and OS (HR = 1.28; 95% CI, 0.23−7.16; p = 0.779) compared to patients with TTS ≤ 5 weeks. For T1b RCC, patients with TTS > 5 weeks had shorter DFS (HR = 2.90; 95% CI = 1.46−5.75; p = 0.002) and OS (HR = 2.49, 95% CI = 1.09−5.70; p = 0.030) than patients with TTS ≤ 5 weeks. Conclusions: Prolonged TTS had no impact on the prognosis of T1a RCC while surgery delayed for over 5 weeks may lead to worse survival in T1b RCC.

Cylindrical Tube Stethoscopes: The Value of Practical Equipment in the Management of Patients with Infectious Diseases.

Background: The COVID-19 pandemic has continued for more than two years since its outbreak. Due to the clinical auscultation needs of doctors when wearing airtight protective clothing, a cylindrical tube stethoscope was proposed to address this problem. However, the idea has been questioned by some experts. Methods: To address these questions, we performed three-part experiments using cylindrical tube stethoscopes. First, we performed laboratory tests to detect the sound intensity from a cylindrical tube stethoscope. Second, we improved the cylindrical tube stethoscope to achieve better results. Third, we revealed the difference in the auscultation effects of the cylindrical tube stethoscope and a conventional professional 3 M stethoscope. Results: From these experiments, we found that a narrow cylindrical tube with a diameter of 4.2 cm and a length of 20 cm equipped with a silicone gasket better auscultation of heart sounds. A cylindrical tube stethoscope and a 3 M stethoscope were used to perform stethoscope tests on 10 volunteers. The alveolar lung sounds were 44.478 decibels vs 49.529 decibels, the heart sounds were 46.631 decibels vs 41.109 decibels, and the intestinal sounds were 40.132 decibels vs 43.787 decibels, respectively. Conclusion: This improved cylindrical tube stethoscope can meet the auscultation requirements for cardiorespiratory and abdominal diagnosis during infectious disease pandemics.

Association of blood glucose level and prognosis of inpatients with coexistent diabetes and COVID-19.

Type 2 diabetes (T2D) increases the risk of coronavirus disease (COVID-19). This study investigates the association between glucose control of COVID-19 patients with T2D in first 7 days after hospital admission and prognosis. A total of 252 infected inpatients with T2D in China were included. Well-controlled blood glucose was defined as stable fasting blood glucose (FBG) levels in the range of 3.9-7.8 mmol/L during first 7 days using indicators of average (FBGA), maximum (FBGM) or first-time (FBG1) FBG levels. The primary endpoint was admission to intensive care unit or death. Hazard ratio (HR) of poorly controlled glucose level group compared with well-controlled group were 4.96 (P = 0.021) for FBGM and 5.55 (P = 0.014) for FBGA. Well-controlled blood glucose levels in first 7 days could improve the prognosis of COVID-19 inpatients with diabetes.

A Postoperative Man with Marfan Syndrome with Palpitations and Chest Pain After Receiving the SARS-CoV-2 Vaccine.

At the moment, the SARS-CoV-19 pandemic is still attacking the health of humanity, and vaccines are the primary health strategy to eradicate this global challenge. So, with the exception of the SARS-CoV-2 vaccine, no vaccine for any disease has been brought to clinical use so quickly. Therefore, even with strict management, it can still bring some special adverse effects. One of the most notable is the adverse cardiovascular reactions to SARS-CoV-2 vaccines. No case reports of individuals with irreversible arrhythmia complications following the SARS-CoV-2 vaccine have been found in the available literature. We report the first case of a postoperative man with Marfan syndrome with atrial fibrillation after receiving the SARS-CoV-2 vaccine.

Sex-based clinical and immunological differences in COVID-19.

BACKGROUND: Males and females differ in their immunological responses to foreign pathogens. However, most of the current COVID-19 clinical practices and trials do not take the sex factor into consideration. METHODS: We performed a sex-based comparative analysis for the clinical outcomes, peripheral immune cells, and severe acute respiratory syndrome coronavirus (SARS-CoV-2) specific antibody levels of 1558 males and 1499 females COVID-19 patients from a single center. The lymphocyte subgroups were measured by Flow cytometry. The total antibody, Spike protein (S)-, receptor binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels were measured by chemiluminescence. RESULTS: We found that male patients had approximately two-fold rates of ICU admission (4.7% vs. 2.7% in males and females, respectively, P = 0.005) and mortality (3% vs. 1.4%, in males and females, respectively, P = 0.004) than female patients. Survival analysis revealed that the male sex is an independent risk factor for death from COVID-19 (adjusted hazard ratio [HR] = 2.22, 95% confidence interval [CI]: 1.3-3.6, P = 0.003). The level of inflammatory cytokines in peripheral blood was higher in males during hospitalization. The renal (102/1588 [6.5%] vs. 63/1499 [4.2%], in males and females, respectively, P = 0.002) and hepatic abnormality (650/1588 [40.9%] vs. 475/1499 [31.7%], P = 0.003) were more common in male patients than in female patients. By analyzing dynamic changes of lymphocyte subsets after symptom onset, we found that the percentage of CD19+ B cells and CD4+ T cells was generally higher in female patients during the disease course of COVID-19. Notably, the protective RBD-specific IgG against SARS-CoV-2 sharply increased and reached a peak in the fourth week after symptom onset in female patients, while gradually increased and reached a peak in the seventh week after symptom onset in male patients. CONCLUSIONS: Males had an unfavorable prognosis, higher inflammation, a lower percentage of lymphocytes, and indolent antibody responses during SARS-CoV-2 infection and recovery. Early medical intervention and close monitoring are important, especially for male COVID-19 patients.

Comparative Characterization and Risk Stratification of Asymptomatic and Presymptomatic Patients With COVID-19.

The identification of asymptomatic, non-severe presymptomatic, and severe presymptomatic coronavirus disease 2019 (COVID-19) in patients may help optimize risk-stratified clinical management and improve prognosis. This single-center case series from Wuhan Huoshenshan Hospital, China, included 2,980 patients with COVID-19 who were hospitalized between February 4, 2020 and April 10, 2020. Patients were diagnosed as asymptomatic (n = 39), presymptomatic (n = 34), and symptomatic (n = 2,907) upon admission. This study provided an overview of asymptomatic, presymptomatic, and symptomatic COVID-19 patients, including detection, demographics, clinical characteristics, and outcomes. Upon admission, there was no significant difference in clinical symptoms and CT image between asymptomatic and presymptomatic patients for diagnosis reference. The mean area under the receiver operating characteristic curve (AUC) of the differential diagnosis model to discriminate presymptomatic patients from asymptomatic patients was 0.89 (95% CI, 0.81-0.98). Importantly, the severe and non-severe presymptomatic patients can be further stratified (AUC = 0.82). In conclusion, the two-step risk-stratification model based on 10 laboratory indicators can distinguish among asymptomatic, severe presymptomatic, and non-severe presymptomatic COVID-19 patients on admission. Moreover, single-cell data analyses revealed that the CD8+T cell exhaustion correlated to the progression of COVID-19.

High Expression of ACE2 and TMPRSS2 at the Resection Margin Makes Lung Cancer Survivors Susceptible to SARS-CoV-2 With Unfavorable Prognosis.

BACKGROUND: 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. METHODS: A single-center, retrospective cohort study was conducted in 65 patients with COVID-19 from Wuhan Huoshenshan Hospital, of which 13 patients were diagnosed with lung cancer. The study was conducted from February 4 to April 11, 2020. RESULTS: During the course of treatment, lung cancer survivors infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) had 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 medium-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. CONCLUSIONS: ACE2 and TMPRSS2 levels were higher at resection margins of lung cancer survivors than those in normal tissues of non-cancerous individuals and may serve as factors responsible for the high susceptibility to COVID-19 among lung cancer survivors. Lung cancer patients diagnosed with COVID-19, including medium-term survivors, have worse outcomes than the general population.

Implications of cardiac markers in risk-stratification and management for COVID-19 patients.

BACKGROUND: COVID-19 has resulted in high mortality worldwide. Information regarding cardiac markers for precise risk-stratification is limited. We aim to discover sensitive and reliable early-warning biomarkers for optimizing management and improving the prognosis of COVID-19 patients. METHODS: A total of 2954 consecutive COVID-19 patients who were receiving treatment from the Wuhan Huoshenshan Hospital in China from February 4 to April 10 were included in this retrospective cohort. Serum levels of cardiac markers were collected after admission. Coronary artery disease diagnosis and survival status were recorded. Single-cell RNA-sequencing and bulk RNA-sequencing from different cohorts of non-COVID-19 were performed to analyze SARS-CoV-2 receptor expression. RESULTS: Among 2954 COVID-19 patients in the analysis, the median age was 60 years (50-68 years), 1461 (49.5%) were female, and 1515 (51.3%) were severe/critical. Compared to mild/moderate (1439, 48.7%) patients, severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. In severe/critical COVID-19 patients, those with abnormal serum levels of BNP (42 [24.6%] vs 7 [1.1%]), hs-TNI (38 [48.1%] vs 6 [1.0%]), α- HBDH (55 [10.4%] vs 2 [0.2%]), CK-MB (45 [36.3%] vs 12 [0.9%]), and LDH (56 [12.5%] vs 1 [0.1%]) had a significantly higher mortality rate compared to patients with normal levels. The same trend was observed in the ICU admission rate. Severe/critical COVID-19 patients with pre-existing coronary artery disease (165/1,155 [10.9%]) had more cases of BNP (52 [46.5%] vs 119 [16.5%]), hs-TNI (24 [26.7%] vs 9.6 [%], α- HBDH (86 [55.5%] vs 443 [34.4%]), CK-MB (27 [17.4%] vs 97 [7.5%]), and LDH (65 [41.9%] vs 382 [29.7%]), when compared with those without coronary artery disease. There was enhanced SARS-CoV-2 receptor expression in coronary artery disease compared with healthy controls. From regression analysis, patients with five elevated cardiac markers were at a higher risk of death (hazards ratio 3.4 [95% CI 2.4-4.8]). CONCLUSIONS: COVID-19 patients with pre-existing coronary artery disease represented a higher abnormal percentage of cardiac markers, accompanied by high mortality and ICU admission rate. BNP together with hs-TNI, α- HBDH, CK-MB and LDH act as a prognostic biomarker in COVID-19 patients with or without pre-existing coronary artery disease.

Evaluation of lung involvement in COVID-19 pneumonia based on ultrasound images.

BACKGROUND: Lung ultrasound (LUS) can be an important imaging tool for the diagnosis and assessment of lung involvement. Ultrasound sonograms have been confirmed to illustrate damage to a person's lungs, which means that the correct classification and scoring of a patient's sonogram can be used to assess lung involvement. METHODS: The purpose of this study was to establish a lung involvement assessment model based on deep learning. A novel multimodal channel and receptive field attention network combined with ResNeXt (MCRFNet) was proposed to classify sonograms, and the network can automatically fuse shallow features and determine the importance of different channels and respective fields. Finally, sonogram classes were transformed into scores to evaluate lung involvement from the initial diagnosis to rehabilitation. RESULTS AND CONCLUSION: Using multicenter and multimodal ultrasound data from 104 patients, the diagnostic model achieved 94.39% accuracy, 82.28% precision, 76.27% sensitivity, and 96.44% specificity. The lung involvement severity and the trend of COVID-19 pneumonia were evaluated quantitatively.

Implications of liver injury in risk-stratification and management of patients with COVID-19.

BACKGROUND: Infection with SARS-CoV-2 has been associated with liver dysfunction, aggravation of liver burden, and liver injury. This study aimed to assess the effects of liver injuries on the clinical outcomes of patients with COVID-19. METHODS: A total of 1520 patients with severe or critical COVID-19 from Huoshenshan Hospital, Wuhan, were enrolled. Chronic liver disease (CLD) was confirmed by consensus diagnostic criteria. Laboratory test results were compared between different groups. scRNA-seq data and bulk gene expression profiles were used to identify cell types associated with liver injury. RESULTS: A total of 10.98% of patients with severe or critical COVID-19 developed liver injury after admission that was associated with significantly higher rates of mortality (21.74%, p < 0.001) and intensive care unit admission (26.71%, p < 0.001). Pre-existing CLDs were not associated with a higher risk. However, fatty liver disease and cirrhosis were associated with higher risks, supported by evidences from single cell and bulk transcriptome analysis that showed more TMPRSS2+ cells in these tissues. By generating a model, we were able to predict the risk and severity of liver injury during hospitalization. CONCLUSION: We demonstrate that liver injury occurring during therapy as well as pre-existing CLDs like fatty liver disease and cirrhosis in patients with COVID-19 is significantly associated with the severity of disease and mortality, but the presence of other CLD is not associated. We provide a risk-score model that can predict whether patients with COVID-19 will develop liver injury or proceed to higher-risk stages during subsequent hospitalizations.

A Rare Giant Midesophageal Diverticulum: Fever is the Only Symptom.

A 55-year-old man was treated at the village hospital with six months medical history of recurrent chills and fever. Due to the lack of imaging examination, antipyretic and anti-infective medications were given. Although symptomatic treatment can relieve fever symptoms, symptoms easily flare up again two to three days after taking the drug. Later, the patient suffered from fever again during the COVID-19 epidemic and was sent to our hospital for isolation and treatment. During this hospitalization, chest CT examination is mandatory for all patients in order to meet the requirements of epidemic prevention and control. This led to the inadvertent discovery of a large cystic solid mass in the right thoracic cavity communicating with the esophageal lumen. The patient was preliminarily diagnosed as giant midesophageal diverticulum after three-dimensional CT image reconstruction of the chest was reviewed. Considering the patient's persistent fever with poor nutritional status, we decided to temporarily place two gastric tubes (diverticulum decompression and gastrointestinal nutrition), and antibiotics were used at the same time as another main treatment. However, after the symptoms eased and nutritional status improved, he refused all further treatment. We believe that this patient's diverticulum is very classic, and the treatment plan is highly integrated with the needs of epidemic prevention and control and achieves a satisfactory therapeutic effect, so we hope to provide colleagues with new diagnosis and treatment enlightenment through this case.

The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery.

SARS-CoV-2 is the pathogen responsible for the COVID-19 pandemic. The SARS-CoV-2 papain-like cysteine protease (PLpro) has been implicated in playing important roles in virus maturation, dysregulation of host inflammation, and antiviral immune responses. The multiple functions of PLpro render it a promising drug target. Therefore, we screened a library of approved drugs and also examined available inhibitors against PLpro. Inhibitor GRL0617 showed a promising in vitro IC50 of 2.1 µM and an effective antiviral inhibition in cell-based assays. The co-crystal structure of SARS-CoV-2 PLproC111S in complex with GRL0617 indicates that GRL0617 is a non-covalent inhibitor and it resides in the ubiquitin-specific proteases (USP) domain of PLpro. NMR data indicate that GRL0617 blocks the binding of ISG15 C-terminus to PLpro. Using truncated ISG15 mutants, we show that the C-terminus of ISG15 plays a dominant role in binding PLpro. Structural analysis reveals that the ISG15 C-terminus binding pocket in PLpro contributes a disproportionately large portion of binding energy, thus this pocket is a hot spot for antiviral drug discovery targeting PLpro.

A basic investigation into the optimization of cylindrical tubes used as acoustic stethoscopes for auscultation in COVID-19 diagnosis.

During the COVID-19 outbreak, the auscultation of heart and lung sounds has played an important role in the comprehensive diagnosis and real-time monitoring of confirmed cases. With clinicians wearing protective clothing in isolation wards, a potato chip tube stethoscope, which is a secure and flexible substitute for a conventional stethoscope, has been used by Chinese medical workers in the first-line treatment of COVID-19. In this study, an optimal design for this simple cylindrical stethoscope is proposed based on the fundamental theory of acoustic waveguides. Analyses of the cutoff frequency, sound power transmission coefficient, and sound wave propagation in the uniform lossless tube provide theoretical guidance for selecting the geometric parameters for this simple cylindrical stethoscope. A basic investigation into the auscultatory performances of the original tube and the optimal tube with proposed dimensions was conducted both in a semi-anechoic chamber and in a quiet laboratory. Both experimental results and front-line doctors' clinical feedback endorse the proposed theoretical optimization.