Hypoxemia In COVID-19 Research Articles

Got the Blues? Mechanisms of Hypoxemia in COVID-19

Got the Blues? Mechanisms of Hypoxemia in COVID-19

Risk factors, mortality, and predictors of survival in COVID-19-associated pulmonary mucormycosis: a multicentre retrospective study from India

ObjectivesTo compare COVID-19-associated pulmonary mucormycosis (CAPM) with COVID-19-associated rhino-orbital mucormycosis (CAROM), ascertain factors associated with CAPM among patients with COVID-19, and identify factors associated with 12-week mortality in CAPM. MethodsWe performed a retrospective multicentre cohort study. All study participants had COVID-19. We enrolled CAPM, CAROM, and COVID-19 subjects without mucormycosis (controls; age-matched). We collected information on demography, predisposing factors, and details of COVID-19 illness. Univariable analysis was used to compare CAPM and CAROM. We used multivariable logistic regression to evaluate factors associated with CAPM (with hypoxemia during COVID-19 as the primary exposure) and at 12-week mortality. ResultsWe included 1724 cases (CAPM [n = 122], CAROM [n = 1602]) and 3911 controls. Male sex, renal transplantation, multimorbidity, neutrophil-lymphocyte ratio, intensive care admission, and cumulative glucocorticoid dose for COVID-19 were significantly higher in CAPM than in CAROM. On multivariable analysis, COVID-19-related hypoxemia (aOR, 2.384; 95% CI, 1.209–4.700), male sex, rural residence, diabetes mellitus, serum C-reactive protein, glucocorticoid, and zinc use during COVID-19 were independently associated with CAPM. CAPM reported a higher 12-week mortality than CAROM (56 of the 107 [52.3%] vs. 413 of the 1356 [30.5%]; p = 0.0001). Hypoxemia during COVID-19 (aOR [95% CI], 3.70 [1.34–10.25]) and Aspergillus co-infection (aOR [95% CI], 5.40 [1.23–23.64]) were independently associated with mortality in CAPM, whereas surgery was associated with better survival. DiscussionCAPM is a distinct entity with a higher mortality than CAROM. Hypoxemia during COVID-19 illness is associated with CAPM. COVID-19 hypoxemia and Aspergillus co-infection were associated with higher mortality in CAPM.

Glucocorticoids in the combination therapy of COVID-19

Since the early months of the SARS-CoV-2 pandemic, the understanding that severe forms of COVID-19 are associated with systemic inflammation has spurred the medical community to greater efforts to evaluate the effect of numerous anti-inflammatory and immunomodulatory therapies. Corticosteroids have a broad and non-specific anti-inflammatory action; they can interfere with mRNA transcription of inflammatory cytokines, reducing the production of inflammatory mediators. Therefore, the use of glucocorticoids will reduce the complications caused by the cytokine storm. On the other hand, immunosuppression in the respiratory epithelium may delay viral clearance and predispose to secondary infections and clinical deterioration. Therefore, WHO does not currently recommend the routine use of corticosteroids in the treatment of patients with COVID-19. The RECOVERY study showed a reduction in mortality with dexamethasone in patients with COVID-19 hypoxemia, as well as an increase in the number of days without mechanical ventilation among critically ill patients. The REMAP-CAP Committee concluded that among patients with severe COVID-19, treatment with a 7-day course of various hydrocortisone dose versus no hydrocortisone resulted in 93 and 80% chances of eliminating the need for respiratory and cardiac support for 21 days. The results of studies conducted show that there was no statistical difference between steroid use and mortality in patients with COVID-19 in the high dose group, while there was statistical difference in the medium dose group. The less 5 days group showed a strong association between reduced mortality in patients with COVID-19 and steroid use, while there were no statistically significant associations in the 5–7 days group and the more than 7 days group. Inhaled forms of corticosteroids deserve attention given their effectiveness and logical use.

Echocardiographic detection of transpulmonary bubble transit during coronavirus-2019 disease (COVID-19)

BackgroundTranspulmonary bubble transit (TPBT) detected with contrast echocardiography is reported as a sign of intrapulmonary arteriovenous shunt. However, its pathological meaning is not clear during coronavirus-2019 disease (COVID-19) related acute respiratory distress syndrome (ARDS). Our aim was to determine the prevalence and clinical significance of TPBT detection during COVID-19 related ARDS. MethodsWe carried out a prospective observational study performed in a high complexity intensive care unit from Argentina. Patients with COVID-19 related ARDS underwent transthoracic echocardiography with saline contrast. Moderate-to-large TPBT was defined as right-to-left passage of at least twelve bubbles to left chambers after at least three cardiac cycles and complete opacification of the right atrium. ResultsWe analyzed the results of 28 patients (24 men and 4 women). Seventy-five percent of the patients received invasive mechanical ventilation. Moderate-to-large TPBT was detected in 1 patient (3.5%). Among the 27 patients without significant TPBT, 23 had no TPBT and 4 had a minor TPBT. TPBT was not associated with invasive mechanical ventilation requirement (p=0.5737) nor in-hospital mortality (p=1). ConclusionsTPBT was not associated with severe hypoxemia or invasive mechanical ventilation requirement, although more studies are needed to further clarify its contributing role in COVID-19 hypoxemia.

Mortality Rates by Age Group and Intubation Status in Hospitalized Adult Patients From 21 United States Hospital Systems During Three Surges of the COVID-19 Pandemic

Mortality Rates by Age Group and Intubation Status in Hospitalized Adult Patients From 21 United States Hospital Systems During Three Surges of the COVID-19 Pandemic

Nitric oxide versus epoprostenol for refractory hypoxemia in Covid-19

ObjectiveTo compare the efficacy and outcomes with inhaled nitric oxide (iNO) and inhaled epoprostenol (iEPO) in patients with refractory hypoxemia due to COVID-19.DesignRetrospective Cohort Study.SettingSingle health system multicenter academic teaching hospitals.Patients OR subjectsAge group of 18–80 years admitted to the medical ICU.InterventionsMechanically ventilated patients with COVID-19 infection, who received either iNO or iEPO between March 1st, 2020, and June 30th, 2020.Measurements and main resultsThe primary outcome was the change in the PaO2/FiO2 (P/F) ratio 1 hour after initiation of pulmonary vasodilator therapy. Secondary outcomes include P/F ratios on days 1–3 after initiation, positive response in P/F ratio (increase of at least 20% in PaO2), total days of treatment, rebound hypoxemia (if there was a drop in oxygen saturation after treatment was stopped), ventilator free days (if any patient was extubated), days in ICU, days to extubation, days to tracheostomy, mortality days after intubation, 30-day survival and mortality. 183 patients were excluded, as they received both iNO and iEPO. Of the remaining 103 patients, 62 received iEPO and 41 received iNO. The severity of ARDS was similar in both groups. Change in P/F ratio at one hour was 116 (70.3) with iNO and 107 (57.6) with iEPO (Mean/SD). Twenty-two (53.7%) patients in the iNO group and 25 (40.3%) in the iEPO group were responders to pulmonary vasodilators n(%)(p = 0.152) (more than 20% increase in partial pressure of oxygen, Pao2), and 18 (43.9%) and 31 (50%) patients in the iNO and iEPO group (p = 0.685), respectively, had rebound hypoxemia. Only 7 patients in the cohort achieved ventilator free days (3 in the iEPO group and 4 in iNO group).ConclusionsWe found no significant difference between iNO and iEPO in terms of change in P/F ratio, duration of mechanical ventilation, ICU, in-hospital mortality in this cohort of mechanically ventilated patients with COVID-19. Larger, prospective studies are necessary to validate these results.

Smartphone-Guided Self-prone Positioning vs Usual Care in Nonintubated Hospital Ward Patients With COVID-19: A Pragmatic Randomized Clinical Trial

BackgroundSafe, effective, and easily implementable treatments that reduce the progression of respiratory failure in COVID-19 are urgently needed. Despite the increased adoption of prone positioning during the pandemic, the effectiveness of this technique on progression of respiratory failure among nonintubated patients is unclear.Research QuestionWhat is the effectiveness of smartphone-guided self-prone positioning recommendations and instructions compared with usual care in reducing progression of respiratory failure among nonintubated patients with COVID-19?Study Design and MethodsAwake Prone Position for Early Hypoxemia in COVID-19 (APPEX-19) is a multicenter randomized clinical trial that randomized nonintubated adults with COVID-19 on < 6 L/min of supplemental oxygen to receive a smartphone-guided self-prone positioning intervention or usual care. The primary outcome was the composite of respiratory deterioration (an increase in supplemental oxygen requirement) or ICU transfer. Using a Bayesian statistical approach, the posterior probability of superiority within each treatment arm (superiority threshold 95%) was calculated.ResultsThe trial was stopped early for slow enrollment. A total of 293 participants were included in the modified intention-to-treat analysis (159 self-prone positioning intervention and 134 usual care). Among participants who self-reported body positioning (n = 139 [70 intervention, 69 usual care]), 71.4% in the intervention arm and 59.4% in the usual care arm attempted prone positioning. Thirty-one participants (posterior mean, 24.7%; 95% credible interval, 18.6-31.4) receiving usual care and 32 participants (posterior mean, 22.1%; 95% credible interval, 16.6-28.1) receiving the self-prone positioning intervention experienced the primary outcome; the posterior probability of superiority for the self-prone positioning intervention was 72.1%, less than the 95% threshold for superiority. Adverse events occurred in 26.9% of participants in the usual care arm and in 11.9% of participants in the intervention arm.InterpretationAmong nonintubated patients with COVID-19, smartphone-guided self-prone positioning recommendations and instructions did not promote strong adherence to prone positioning.Clinical Trial RegistrationClinicalTrials.gov; No.: NCT04344587; URL: www.clinicaltrials.gov.

Critical role of nitric oxide in impeding COVID-19 transmission and prevention: a promising possibility.

COVID-19 is a serious respiratory infection caused by a beta-coronavirus that is closely linked to SARS. Hypoxemia is a symptom of infection, which is accompanied by acute respiratory distress syndrome (ARDS). Augmenting supplementary oxygen may not always improve oxygen saturation; reversing hypoxemia in COVID-19 necessitates sophisticated means to promote oxygen transfer from alveoli to blood. Inhaled nitric oxide (iNO) has been shown to inhibit the multiplication of the respiratory coronavirus, a property that distinguishes it from other vasodilators. These findings imply that NO may have a crucial role in the therapy of COVID-19, indicating research into optimal methods to restore pulmonary physiology. According to clinical and experimental data, NO is a selective vasodilator proven to restore oxygenation by helping to normalize shunts and ventilation/perfusion mismatches. This study examines the role of NO in COVID-19 in terms of its specific physiological and biochemical properties, as well as the possibility of using inhaled NO as a standard therapy. We have also discussed how NO could be used to prevent and cure COVID-19, in addition to the limitations of NO.

Silent Hypoxia in COVID-19 Pneumonia: State of Knowledge, Pathophysiology, Mechanisms, and Management.

Patients with COVID-19 often present with life-threatening hypoxemia without dyspnea or signs of respiratory distress. Termed silent or happy hypoxia, it has puzzled clinicians and challenged and defied our understanding of normal respiratory physiology. A range of host- and pathogen-related factors appears to contribute to its development, including SARS-CoV-2's ability to produce different COVID-19 phenotypes; induce endothelial damage and elicit a vascular distress response; invade cells of the central nervous system and disrupt normal interoception and response; and modulate transcription factors involved in hypoxic responses. Because hypoxemia in COVID-19 is associated with increased mortality risk and poorer survival, early detection and prompt treatment is essential to prevent potential complications. Interventions to prevent hypoxemia and improve oxygen delivery to the blood and the tissues include home pulse-oximetry monitoring, optimization of patient positioning, judicious use of supplemental oxygen, breathing control exercises, and timely and appropriate use of ventilatory modalities and adjuncts.

Imaging Pulmonary Blood Vessels and Ventilation-Perfusion Mismatch in COVID-19.

COVID-19 hypoxemic patients although sharing a same etiology (SARS-CoV-2 infection) present themselves quite differently from one another. Patients also respond differently to prescribed medicine and to prone Vs supine bed positions. A severe pulmonary ventilation-perfusion mismatch usually triggers moderate to severe COVID-19 cases. Imaging can aid the physician in assessing severity of COVID-19. Although useful for their portability X-ray and ultrasound serving on the frontline to evaluate lung parenchymal abnormalities are unable to provide information about pulmonary vasculature and blood flow redistribution which is a consequence of hypoxemia in COVID-19. Advanced imaging modalities such as computed tomography, single-photon emission tomography, and electrical impedance tomography use a sharp algorithm visualizing pulmonary ventilation-perfusion mismatch in the abnormal and in the apparently normal parenchyma. Imaging helps to access the severity of infection, lung performance, ventilation-perfusion mismatch, and informs strategies for medical treatment. This review summarizes the capacity of these imaging modalities to assess ventilation-perfusion mismatch in COVID-19. Despite having limitations, these modalities provide vital information on blood volume distribution, pulmonary embolism, pulmonary vasculature and are useful to assess severity of lung disease and effectiveness of treatment in COVID-19 patients.

Causes of Hypoxemia in COVID-19.

The global pandemic of a new coronavirus disease (COVID-19) has posed challenges to public health specialists around the world associated with diagnosis, intensive study of epidemiological and clinical features of the coronavirus infection, development of preventive approaches, therapeutic strategies and rehabilitation measures. However, despite the successes achieved in the study of COVID-19 pathogenesis, many aspects that aggravate the severity of the disease and cause high mortality of patients remain unclear. The main clinical manifestation of the new variant of SARS-CoV-2 virus infection is pneumonia with massive parenchymal lesions of lung tissue, diffuse alveolar damage, thrombotic manifestations, disruption of ventilation-perfusion relationships, etc. However, symptoms in patients hospitalized with COVID pneumonia show a broad diversity: the majority has minimal manifestations, others develop severe respiratory failure complicated by acute respiratory distress syndrome (ARDS) with rapidly progressing hypoxemia that leads to high mortality. Numerous clinical data publications report that some COVID pneumonia patients without subjective signs of severe respiratory failure (dyspnea, “air hunger”) have an extremely low saturation level. As a result, there arises a paradoxical condition (called “silent hypoxia” or even “happy hypoxia”) contradicting the very basics of physiology, as it essentially represents a severe life-incompatible hypoxemia which lacks respiratory discomfort. All this raises numerous questions among professionals and has already ignited a discussion in scientific publications concerned with the pathogenesis of COVID-19. Respiratory failure is a complex clinical problem, many aspects of which remain controversial. However, according to the majority of authors, one of the first objective indicators of the clinical sign of respiratory failure are hypoxemia-associated changes in external respiration. This review addresses some possible causes of hypoxemia in COVID-19.

DEVELOPMENT OF METHEMOGLOBINEMIA IN A PATIENT WITH COVID-19 PNEUMONIA

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: The World Health Organization officially declared COVID-19 as a pandemic in March 2020. Since then, it has caused more than 1.5 million deaths and has affected more than 68 million people worldwide (1). Methemoglobinemia is a very rare and potentially life-threatening condition. Congenital methemoglobinemia is caused by a deficiency in cytochrome b5 reductase (Cyb5R) while acquired is caused by exposure to an oxidizing agent such as chloroquine or dapsone. We present a case of a critically ill patient with COVID-19 pneumonia who developed methemoglobinemia without an identifiable cause. CASE PRESENTATION: A 64-year-old gentleman with past medical history of hypertension presents to the emergency department (ED) with chief complaints of shortness of breath and myalgias for the past 3 days. In the ED, patient was found to tachycardic at 121 beats/minute, tachypneic at 40 breaths/minute, and febrile at 38.6° Celsius. He was found to have elevated COVID-19 labs which included C-reactive protein, lactate dehydrogenase, ferritin, creatine phosphokinase, d-dimer in addition to elevated BUN 53 mg/dL and creatinine 2.92 mg/dL. His COVID-19 PCR resulted positive and was placed on bilevel positive airway pressure (BPAP) for his respiratory distress and transferred to the medical intensive care unit (MICU) for further monitoring. He was started on broad spectrum antibiotics with vancomycin and cefepime along with dexamethasone and remdesivir. Within 24 hours of admission, patient required mechanical ventilation for worsening hypoxemia. Furthermore, his kidney function continued to decline and required continuous renal replacement therapy. His oxygen requirements improved until hospital day 10;where he developed methemoglobinemia measuring 11.8%. Patient was then given methylene blue 1mg/kg and 1.5 grams of ascorbic acid. Hematology was consulted for emergent exchange transfusion as he developed hemolysis but was deemed too unstable and unlikely to benefit. Patient subsequently went into multisystem organ failure and died on hospital day 12. DISCUSSION: To date, there has only been one reported case of COVID-19 complicated by methemoglobinemia without an identifiable cause (2). Our patient tested negative for glucose-6-phosphate dehydrogenase (G6PD) deficiency and a full medication reconciliation was performed without an identifiable cause. However, there have been 10 cases reported that were either associated with use of an oxidizing agent such as hydroxychloroquine or G6PD deficiency (3–6). Therefore, clinicians should be cognizant of the rising cases of methemoglobinemia and COVID-19. CONCLUSIONS: In the setting of COVID-19 pneumonia requiring mechanical ventilation with refractory hypoxemia, clinicians should be mindful that methemoglobinemia may be a contributing factor. Therefore, in the setting of refractory hypoxemia in COVID-19, measuring methemoglobin levels should be considered. REFERENCE #1: 1) Home - Johns Hopkins Coronavirus Resource Center. Accessed December 6, 2020. https://coronavirus.jhu.edu/2) Lopes DV, Lazar Neto F, Marques LC, Lima RBO, Brandao AAGS. Methemoglobinemia and hemolytic anemia after COVID-19 infection without identifiable eliciting drug: A case-report. IDCases. 2021;23:e01013. doi:10.1016/j.idcr.2020.e01013 REFERENCE #2: 3) Faisal H, Bloom A, Gaber AO. Unexplained Methemoglobinemia in Coronavirus Disease 2019: A Case Report. AA14(9):e01287. doi:10.1213/XAA.00000000000012874) Choo SY. Letters to the Editor in Therapeutic Apheresis and Dialysis Rapidly rising methemoglobinemia in a patient with severe COVID-19 treated successfully with red cell exchange transfusion Running Title: Red Cell Exchange for COVID-19 Methemoglobinemia. doi:10.1111/tap.13598 REFERENCE #3: 5) Naymagon L, Berwick S, Kessler A, Lancman G, Gidwani U, Troy K. The emergence of methemoglobinemia amidst the COVID-19 pandemic. Am J Hematol. 2020;95(8):E196-E197. doi:10.1002/ajh.258686) Palmer K, Dick J, French W, Floro L, Ford M. ethemoglobinemia in patient with g6pd deficiency and sars-cov-2 infection. Emerg Infect Dis. 2020;26(9):2279-2281. doi:10.3201/eid2609.202353 DISCLOSURES: No relevant relationships by Paul Nguyen, source=Web Response No relevant relationships by Jonathan Pickos, source=Web Response No relevant relationships by Aryan Shiari, source=Web Response No relevant relationships by Ayman Soubani, source=Web Response

Oxyhemoglobin concentrations do not support hemoglobinopathy in COVID-19

Based on computerized modeling studies, it has been postulated that the severe hypoxemia in COVID-19 may result from impaired oxygen carrying capacity on hemoglobin. Standard pulse oximetry may not detect hypoxemia resulting from hemoglobinopathy, therefore hemoglobin co-oximetry is needed to evaluate this divergence. In a clinical data analysis of a multicenter cohort of hospitalized patients with COVID-19, we found a minimal effect, less than 1%, on the correlation between oxyhemoglobin concentration and predicted oxygen saturation in the presence of COVID-19 infection. This effect is unlikely to explain the clinically significant hypoxia in COVID-19 patients.

Prevalence and outcome of silent hypoxemia in COVID-19.

In the early stages of COVID-19 pneumonia, hypoxemia has been described in absence of dyspnea ("silent" or "happy" hypoxemia). Our aim was to report its prevalence and outcome in a series of hypoxemic patients upon Emergency Department admission. In this retrospective observational cohort study we enrolled a study population consisting of 213 COVID-19 patients with PaO<inf>2</inf>/FiO<inf>2</inf> ratio <300 mmHg at hospital admission. Two groups (silent and dyspneic hypoxemia) were defined. Symptoms, blood gas analysis, chest X-ray (CXR) severity, need for intensive care and outcome were recorded. Silent hypoxemic patients (68-31.9%) compared to the dyspneic hypoxemic patients (145-68.1%) showed greater frequency of extra respiratory symptoms (myalgia, diarrhea and nausea) and lower plasmatic LDH. PaO<inf>2</inf>/FiO<inf>2</inf> ratio was 225±68 mmHg and 192±78 mmHg in silent and dyspneic hypoxemia respectively (P=0.002). Eighteen percent of the patients with PaO<inf>2</inf>/FiO<inf>2</inf> from 50 to 150 mmHg presented silent hypoxemia. Silent and dyspneic hypoxemic patients had similar PaCO<inf>2</inf> (34.2±6.8 mmHg vs. 33.5±5.7 mmHg, P=0.47) but different respiratory rates (24.6±5.9 bpm vs. 28.6±11.3 bpm respectively, P=0.002). Even when CXR was severely abnormal, 25% of the population was silent hypoxemic. Twenty-six point five percent and 38.6% of silent and dyspneic patients were admitted to the ICU respectively (P=0.082). Mortality rate was 17.6% and 29.7% (log-rank P=0.083) in silent and dyspneic patients. Silent hypoxemia is remarkably present in COVID-19. The presence of dyspnea is associated with a more severe clinical condition.

The Importance of Happy Hypoxemia in COVID-19.

BackgroundNowadays, the new coronavirus (SARS-CoV-2) and its complications are one of the main concerns of the world. One of the most severe complications of COVID-19 is hypoxemia.ObjectivesThis study aimed to assess the importance of happy hypoxemia in COVID-19.MethodsWe systematically searched web of science, PubMed, and Google scholar databases to find articles related to COVID-19 and happy hypoxemia.ResultsCOVID-19 causes a type of hypoxemia named silent (happy) hypoxemia, which has an atypical clinical presentation. This type of hypoxemia has not been noted before in viral pneumonia, and there is no specific treatment for this serious complication. Patients with silent hypoxemia may develop severe hypoxemia without dyspnea and with near-normal lung compliance. These patients are awake, calm, and responsive. Although their lungs are not oxygenated efficiently, they are alert and cooperative. Their condition may be deteriorated rapidly without warning and causes death.ConclusionsAccording to the findings, paying attention to happy hypoxemia is important for improving the health status of COVID-19 patients.

Pneumolysis and "Silent Hypoxemia" in COVID-19.

COVID-19 can evolve to a severe lung compromise with life-threatening hypoxemia. The mechanisms involved are not fully understood. Their understanding is crucial to improve the outcomes. Initially, past-experience lead to the implementation of standardized protocols assuming this disease would be the same as SARS-CoV. Impulsive use of ventilators in extreme cases ended up in up to 88% fatality. We compare medical and physiological high altitude acute and chronic hypoxia experience with COVID-19 hypoxemia. A pathophysiological analysis is performed based on literature review and histopathological findings. Application of the Tolerance to Hypoxia formula = Hemoglobin/PaCO2 + 3.01 to COVID-19, enlightens its critical hypoxemia. Pneumolysis is defined as progressive alveolar-capillary destruction resulting from the CoV-2 attack to pneumocytes. The adequate interpretation of the histopathological lung biopsy photomicrographs reveals these alterations. The three theoretical pathophysiological stages of progressive hypoxemia (silent hypoxemia, gasping, and death zone) are described. At high altitude, normal low oxygen saturation (SpO2) levels (with intact lung tissue and adequate acid–base status) could be considered silent hypoxemia. At sea level, in COVID-19, the silent hypoxemia starting at SpO2 ≤ 90% (comparable to a normal SPO2 {88–92%} at 3500 m) suddenly evolves to critical hypoxemia. This, as a consequence of progressive pneumolysis + inflammation + overexpressed immunity + HAPE-type edema resulting in pulmonary shunting. The proposed treatment is based on the improvement of the Tolerance to Hypoxia (Hemoglobin factor), oxygen therapy, inflammation reduction, antibiotics, antitussives, rehydration & anticoagulation if required. Understanding the pathophysiology of COVID-19 may assist in this disease's management.

Rethinking COVID-19 'pneumonia' - is this primarily a vaso-occlusive disease, and can early anticoagulation save the ventilator famine?

Rethinking COVID-19 'pneumonia' - is this primarily a vaso-occlusive disease, and can early anticoagulation save the ventilator famine?

Happy Hypoxemia in COVID-19-A Neural Hypothesis.

Many COVID-19 patients are presenting with atypical clinical features. Happy hypoxemia with almost normal breathing, anosmia in the absence of rhinitis or nasal obstruction, and ageusia are some of the reported atypical clinical findings. Based on the clinical manifestations of the disease, we are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of the nucleus tractus solitarius may be the reason for happy hypoxemia in COVID-19 patients.

"Silent" hypoxemia in COVID-19: Hunt for the shunt!

Dear Editor, We read with interest the exemplary description of the respiratory and cardiovascular effects of COVID-19 infection by Kapoor, featured recently in the journal.[1] While we appreciate the elaboration upon the multi-faceted spectrum of the novel SARS-Cov-2 pneumonia in the index article, the lack of dyspnea (”silent”or “happy” hypoxemia) and plummeting desaturation in this cohort of patients, continue to bewilder and baffle the fraternity at large. In this context, we wish to impress upon the very interesting hypothesis recently put forth by Fisher, regarding the role of the unanticipated opening of an underlying patent foramen ovale (PFO) in explaining this mysterious hypoxemia.[2] Nevertheless, a number of factors surrounding this hypothesis merit attention: (i) Considering the existing literature on the magnitude of intra-thoracic shunt in acute respiratory distress syndrome (ARDS)[2] and given the astonishingly high frequency of a probe-patent PFO (20-25%)[3]; the intra-cardiac right-to-left (R-L) shunt could add significantly to the intrapulmonary shunt in aggravating the systemic hypoxemia ahead of the deterioration in the respiratory mechanics. (ii) In addition, Gattinoni and colleagues have also adequately highlighted the importance of estimating the shunt fraction in the COVID-related ARDS (as they describe it as a not so “typical” ARDS).[4] (iii) Moreover, the accompanying pathological elevation of right atrial pressures (RAP) (in background of pulmonary artery hypertension owing to the ongoing inflammatory process) is expected to promote the intra-cardiac R-L shunting (precluded in health by the physiologically higher left atrial pressures compared to RAP) which is unlikely to respond well to oxygenation wherein positive pressure ventilation will only make the matter worse.[15] While the debate on the mechanisms of “silent” hypoxemia continues to snowball with every passing day of the pandemic, acknowledgement to the shunt patho-physiology and bedside echocardiographic exploration for PFO cannot only provide anatomico-physiological clues to the deteriorating oxygen saturation rather the degree of R-L shunt can also guide the monitoring of the concomitant pulmonary vasodilator therapy with the potential of benefitting a considerable number of critically ill COVID-19 patients. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.