Mayo Clinic hospitalists M. Caroline Burton, M.D. , and Chandrasagar (Sagar) Dugani, M.D., Ph.D ., discuss management of patients with COVID-19 from the hospitalist perspective. They review a standard approach to triage, how to identify risk factors for severe disease, and the therapeutic management for optimal disease control.
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Welcome to Mayo Clinic Cove in 19 expert insights and strategies. The following activity is supported in part by an independent medical education grant from Pfizer Inc and is in accordance with a C CMI guidelines. My name is Caroline Burton, and I'm here today with soccer Do Ghani to talk to you about Cove in 19 specifically about hospitalist management of the Kovar 19. Positive patient. We have no disclosures The objectives for today to review the standard approach to triage in the management of patients with Cove in 19 infection. Identify risk factors for severe disease. Describe the therapeutic management of Kobe 19 using antivirals and immuno modulators and to recognize additional considerations of Koba 19 Disease Management Cove in 19 is a respiratory illness caused by a novel zoonotic pathogen. SARS. Cov to belongs to a family of large enveloped RNA viruses that have a crown like appearance. The first case was reported in December of 2000 and 19 in Wuhan, China. In March of 2020 the World Health Organization declared Cove in 19 as a global pandemic. The virus transmitted between humans by respiratory droplets, aerosols and faux mites, Covad 19 symptoms typically start between four and 14 days after exposure. Common symptoms are fever, dry cough, shortness of breath and fatigue that can also be sore throat, diarrhea, nausea and vomiting, diarrhea and loss of smell and taste. There may be G I symptoms in up to 10% of patients. Most cases of Covad 19 though, are mild, with approximately 80% of them managed with supportive care. In the outpatient setting, around 20% of patients develop moderate to severe pneumonia that is best managed in the hospital. All patients with Kovar 19 should be risk. Stratus Fied four Disease progression Risk factors for disease progression are older age diabetes mellitus, chronic lung disease, hypertension, chronic liver and kidney disease, body mass index greater than 40 immuno compromised status and cardiovascular disease. Disease course most often is a symptomatic to mild, but in some cases disease course is moderate to severe. Moderate disease is manifest by a compromise gas exchange, but 02 saturation is remain greater than 93%. Severe disease manifest by respiratory rate greater than 30 oxygen saturation of less than or equal to 93% on room air. A pho to toe F i 02 ratio of less than 300 are pulmonary infiltrates, involving more than 50% of the lung. Importantly, respiratory failure may occur precipitously, often during the second week of illness, so these patients need to be monitored quite closely. Laboratory and radiographic evaluation for patients with mild cova 19 disease is not recommended upon hospitalization for moderate to severe pneumonia from Cove in 19. The following studies air recommended CBC C reactive protein, D dime er, an assessment of liver and renal function, Pro calcitonin, interleukin six and Chariton BMP troponin glucose six. Phosphate di hydrogen knows pro thrombin time soluble fiber and monomer complex. Common laboratory findings among hospitalized patients with cova 19 include limp, a pina elevated liver, trans emanates levels elevated like take G. I draw Jenness levels and elevated inflammatory markers as well as abnormalities and coagulation Test PT PTT. Indeed, Eimer should be checked on a hospitalization and every day or every other day if elevated Heidi diner levels and severe limp opinion have been associated with critical illness or mortality. Echocardiograms on patient with Cove in 19 is not recommended. However, there may be developments in the clinical course that warrant an echocardiogram including increasing troponin levels with him. A dynamic compromise or other cardiovascular findings such as cardiomyopathy in hospitalized patients with Kovar 19 Respiratory co infection is uncommon, but if suspected patients may be tested, particularly for influenza, chest X ray may be normal in early or mild disease in common. Radiographic findings include consolidation and ground glass opacity. Ease with bilateral peripheral or lower lungs. Oh, distributions. Portable chest X rays should be obtained in patients with moderate to severe respiratory symptoms in order to assess the severity of pneumonia and identify other processes. Electrocardiogram is important if utilizing therapies that prolonged the QTC interval Infectious disease consultation upon admission is strongly encouraged. Approximately 5% of patients with Koba 19 progressed. A critical illness characterized the hyper inflammatory syndrome. Clinical features include hypotension shock, respiratory failure and multi organ failure. Acute respiratory distress syndrome is a major complication in patients with severe disease and can occur shortly after onset of Dis MIA. Other complications include a arrhythmias and acute cardiac injury resulting in shock. Trumbo and Bolic complications, including pulmonary embolism and acute stroke, have also been reported. Infection control interventions to reduce transmission of cova, 19 include Universal source control, for example, covering the nose and mouth to contain respiratory secretions and early identification and isolation of patients with suspected disease. All patients should be screened for clinical manifestations consistent with Koven. 19. Prior to entry into a health care facility, health care workers should monitor themselves for fever and symptoms of Cove in 19 and stay at home if ill health care workers should also be educated about the need to report all known or possible unprotected exposures to Cove in 19 all health care workers who entered the room of a patient was suspected or confirmed. Cova, 19 should wear personal protective equipment to reduce the risk of exposure, Standard PP. For patients with suspected or confirmed cove in 19 includes the use of gown gloves, a respirator or medical mask, and I, or face protection. And in 95 or other respiratory respirator that offers a higher level of protection should be worn instead of a medical mask. During heiress law generating procedures and certain types of environmental cleaning, single patient dedicated medical equipment, such a stethoscopes and thermometers should be used. The number of individuals entering the room of a patient with Kogan, 19 should be limited for I or face protection goggles or a disposable face shield that covers the front and sides. The face should be used. Glasses alone are not sufficient. A panel of US physicians, statisticians and other experts has developed treatment guidelines for Cove in 19. These guidelines are based on published and preliminary data and the clinical expertise of the Panelists. The recommendations in these guidelines are based on scientific and expert opinion. The letters A, B and C indicates strength of recommendations with Letter A being the strongest in Roman numerals 12 and three. Regarding the quality of evidence to support the recommendation, there are no FDA approved drugs for the treatment of covert. 19 current treatment modalities include antiviral therapy in immune based therapy. Antiviral therapy, consisting of room disappear, has been found superior to placebo and short and time to recovery and adults hospitalized with Koven, 19 infection and evidence of lower respiratory tract infection. Ren Disappear is recommended for hospitalized patients who require low flow supplemental oxygen and have severe cove in 19. Ram disappear is administered intravenously and the duration of therapy This five days there is insufficient data regarding duration of therapy for hospitalized patients on mechanical ventilation or ECMO. Some have recommended treatment for these patients up to 10 days. Duration of therapy can be extended up to 10 days if there is no clinical improvement or the patient is on mechanical ventilation or ECMO. Overall, the evidence for a clinical benefit of room disappear is strong for patients with severe disease who do not require high flow supplemental oxygen or ventilatory support. If the patient is ready to discharge prior to completing the course of RAM disappear, it can be discontinued. In the United States, the FDA has issued an emergency use authorization for remedy severe for hospitalized Children and adults With Koven 19 regardless of disease severity, there is insufficient data for the panel to recommend for or against the treatment of patients with mild or moderate cova 19 using room disappear. The recommended dose for adults weighing 40 g or higher is a single loading dose of 200 mg on day one, followed by once daily dose of 100 mg on today. Well, I made a mistake again on Slide 16 so I'm going to start at the top of Slide 16 The recommended dose for adults weighing 40 g or higher is a single loading dose of 200 mg on day one, followed by a once daily dose of 100 mg from day to through day five. Ram disappear is an ivy infusion administered over 30 to 120 minutes. The effect of RAM de severe on renal function is unknown. However, it is not recommended that patients with a GF are less than 30 be administered ram de severe unless the potential benefit outweighs the risk. RAM disappear is not recommended in patients with an Ally nine amino transfer, its level greater than or equal to five times the upper limit of normal. The medication should be discontinued if the rises above this level during treatment or if there are other signs of liver injury remedy Severe should not be used with hydroxy claure, Quinn or Claure Quinn. Because of pharmacologic effects, the panel recommends against using high truck seek Laura Quinn or Clara Quinn in hospitalized patients, given the lack of clear benefit and the potential for toxicity. In June of 2020 the U. S. FDA revoked its emergency use authorization for these agents in patients with severe Cova, 19. The panel also recommends against using HIV protease inhibitors because of unfavorable pharma code dynamics, and clinical trials have not demonstrated a benefit. While LaPierre, near Rattana Veer, has in vitro activity against Kobe, 19 and is currently being evaluated in clinical trials for Cove in 19 it appears tohave a minimal role in the treatment of hospitalized patients with Cove in 19 infection convalescent plasma obtained from individuals who have recovered from Cove in 19 infection as a potential option for therapy in hospitalized patients. It is possible convalescent plasma provides clinical benefit because it contains high neutralizing antibody tigers and can be given early in the course of disease. In patients who do not require mechanical ventilation. Data on the efficacy from randomized clinical trials are lacking In the United States. The FDA granted emergency use authorization for hospitalized patients with cova. 19 international and national clinical trials of convalescent plasma are ongoing. Markedly elevated inflammatory markers, including I'll six, are associated with critical and fatal Covad 19. Blocking the inflammatory pathway has been hypothesized to prevent disease progression. Several agents that target the Aisle six pathway had been evaluated in randomized trials for treatment of Cove in 19 as well as I a one pathway inhibitors. There is insufficient data recommended either for or against the use of these agents at this time, and their use may be associated with an increased risk of secondary infections. Dexamethasone is recommended for severely ill patients with cove in 19 who are on supplemental oxygen or ventilatory support. Dexamethasone can be used at a dose of 6 mg daily for 10 days or until discharge, whichever is shorter. If Dex a methadone, is unavailable, it is reasonable to use other glucocorticoids at equivalent doses, including hydrocortisone metal, pregnant alone and pregnant. Soon. Data from randomized trials overall support the role of glucocorticoids for severe code. In 19 there was no benefit for patients who did not require oxygen or ventilatory support. Orel Korca store. It's Orel corticosteroid therapy use and prior to Koba 19 Diagnosis for another underlying condition should not be discontinued and on a case by case basis, these patients may require stress those steroids. Respiratory care should involve targeting peripheral oxygen saturation to greater than or equal to 90% self Pronin position of hospitalized patients is potentially beneficial while receiving oxygen or non invasive modalities such as high flow oxygen delivered via nasal cannula or noninvasive ventilation. Nebulizer therapy should be reserved for acute broncho spasm. For most persons, isolation precautions congenitally be discontinued at 10 days after symptom onset and IT resolution of fever for at least 24 hours. A limited number of persons with severe illness may produce replication competent viruses up to 10 days. That may warrant extending duration of isolation precautions for up to 20 days after onset of symptoms. For persons who never developed symptoms, isolation and other precautions can be discontinued 10 days after the date of the first positive PCR test. Dr Ghani will now discuss other considerations in the hospitalist management of Covad 19. In the previous segment, we reviewed the hospitalist management strategies off covert positive patients. In this segment, we will review non covert 19 issues in the hospitalist management of covert 19 positive patients. There are several non covert 19 issues to consider, such as management off traumatic events, use of chronic medications, care of geriatric patients, transition to higher level care, including the intensive care unit, or ICU. The role of palliative care team based collaborative care and visitor policies in addition, there are several issues to consider in discharge, planning and follow up, including appropriate discharge criteria. Discharging a patient home or to another care facility. The use off discharge checklists. Discharging a patient against medical advice, patient follow up and quarantine and care off patient caregivers. Management off traumatic events among covert 19 positive patients has received a significant amount of attention because covert 19 positive patients are at higher risk off hyper curricula ability as well as bleeding. Several studies have shown that the general inflammatory state associated with covert 19 infection may predispose patients to arterial and venous thrombosis events. There may be several ideologies for the increased risk, but are thought to include increased venous Stasis, inflammation, platelet activation and endothelial dysfunction. This figure is from a recent review paper on Covert 19 and Traumatic and Trumbo M Bolic disease. This pyramid shows the potential for increased risk off Venus Trumbo embolism and adverse outcomes, depending on the burden off covert 19. At the bottom off the pyramid, we have an uninfected population, a section off. This group may be asymptomatic and untested, but may carry the cove in 19 virus. They serve as vectors for the infection. A section above them may be tested and diagnosed with co vid despite being asymptomatic. As we move up the pyramid, we have patients with mild covert 19 infection, moderate to severe covert 19 infection and, in more serious cases, covert 19 infection that leads to death as we move up the pyramid. Several factors contribute to increased hyper coagulate, bility and bleeding, including patient age, decreased mobility or being bedridden. He must static abnormalities and other patient Colmar abilities in the absence off contra indications, which should be evaluated individually for patients. VT. A prophylaxis is recommended as you move from the base to the tip off the pyramid. The risk off traumatic events depends on individual risk factors and him a static abnormalities, as shown in this schematic under panel A. These risk factors include acute illness, being bedridden or having reduced mobility, individual genetic factors which are poorly understood at this stage fever, diarrhea and other risk factors. As a consequence of these risk factors, there may be an inflammatory response, as you heard in an earlier segment of this presentation endothelial dysfunction. In addition to superimposed infection, the inflammatory state can be identified by the presence of inflammatory cytokines. As discussed earlier in this presentation, many of these site A kinds are the targets off investigational therapies for covert 19 infection in Panel B. Hema Static abnormalities include pulmonary micro thrum by intravascular coagulation, pithy myocardial injury and increase in cardiac biomarkers in panel. See, depending on the interaction between risk factors and Hema static abnormalities, they result in different clinical outcomes, including Venus Trumbo Embolism, Myocardial Injury and D. I. C. Several studies have contributed to our understanding off the risk off hyper coagulation and bleeding in covert 19 patients. Covert 19 infection is associated with a higher risk off VT. Few studies have shown that among non I see you patients with DVT or P E symptoms, approximately 6% had a DVT, or P E. Approximately 50% of VT events were documented within 24 hours after admission. Among non issue patients admitted greater than 48 hours, an estimated 20% had a DVT. In addition to Venus Trumbo, Embolism Cove in 19 is also associate ID with ah high risk off arterial thrombosis, including increased risk of stroke, limb ischemia and myocardial infarction. Cove in 19 is also associated with a high risk off microvascular thrombosis as well as, ah, high risk off bleeding. The risk associated with bleeding is less frequent than for traumatic events, and the mechanisms are not well understood. These may involve D. I C or result from other anti coagulation related complications. The recommended testing for Ah hyper coagulate ble state may vary by institutional practice. In many instances, the following blood tests are recommended and routinely obtained. Complete blood count, which is characterized in covert 19 infection by Trumbull Site Opinion and Lymph Opinion di Dimmer and Fiber. No gin, which are typically elevated in corporate 19 infection. The coagulation profile off in our M P T. T are also typically elevated in covert 19 infections. The image ing obtained will depend on the clinical presentation and suspicion, as well as patient factors, but typically include ultrasound toe, identify, deep vein thrombosis and CT pulmonary angiography to identify pulmonary emboli. The management off traumatic events can be done in several ways. War ferrin or direct oral anticoagulants can be used, and if they were used prior to admission, they can be continued during the patient's hospital stay. If that is not relevant, to the patient, then active or prior. And if the patient had active or prior heparin induced Trumbo side opinion or hit, then we have two options based on the patient's creatinine clearance. If the creatinine clearance is greater than 30 mL per minute, Fonda paradox is a therapeutic option. If the clearance is less than 30 mL per minute, the hospitalists may require consultation with he mythology specialists to consider other therapies, including S. C. D. S. In instances where there are contraindications to pharmacologic prophylaxis, Ah, consultation with human ethology is strongly considered. If none of the above are relevant to the patient, then the hospitalists may consider in Oxy parent daily or twice daily, depending on the patient's body. Mass index, which is our preferred therapy or unfashionable, did happen again, dosed based on the patient's weight or body mass index. While the management off traumatic events is important, several other chronic medications required careful review. ACE inhibitors received prominent and early attention in the Cove in 19 Pandemic, as there was suspicion that Cove in 19 patients on Ace's inhibitors may have adverse events or outcomes. Compared to patients not on Ace's inhibitors, this schematic is from a recent review paper on a Sinha bitters and the Cove in 19 infection. In the right side of the picture, we see a schematic for the well known function Off Ace. It converts angiotensin one to angiotensin two angiotensin two, then binds to angiotensin two type one receptor, leading to lung injury. There's a constriction and vascular permeability, as is well known. ACE inhibitors interfere with this process and provide a protective benefit to patients. Ace to is shown in purple and is a counter regulator off this process. ACE inhibitors do not directly affect Ace, too. However, the covert 19 virus binds to ace, too. And since a stew is a counter regulator, there was concerned that Cove in 19 patients on Ace's inhibitors might have worse outcomes. And although the suspicion has been extensively studied in the literature to date, there is no compelling evidence that this is true in corporate 19 patients. Angiotensin receptor blockers, which again is shown in the schematic as interfering between the association off angiotensin two and its receptor ARBs, may have a protective effect in covert 19 positive patients. At present, there is no evidence to initiate or discontinue these medications. The decision to initiate or discontinue should be based on the usual indications. Example. Management of blood pressure, my cardio infarction, kidney injury, etcetera. Our knowledge on the interaction of ACE inhibitors, ARBs and covert 19 virus is increasing. Future studies may provide more information on these topics. Statins and immune modulators are an important class off chronic medications that should be considered. Statins have anti traumatic and anti inflammatory effects. Despite this, there is no clear evidence to initiate statins in Staten naive covert patients, given the high frequency off other co mobility's, such as diabetes and cardiac disease. Among cove in 19 patients, guidelines currently recommend continuing statins. Corticosteroids also have anti inflammatory effects. However, there is concern that they may prolong viral replication. Initial studies show cortical steroids may be beneficial in a subset of covert 19 patients. As you heard in an earlier segment off this presentation, the use of other immune modulators for non covert health conditions, such as rheumatoid logic conditions, require a case by case evaluation and consultation with experts. Non steroidal anti inflammatory drugs also play an important role in management off non co vid 19 conditions. Initial studies concerning for adverse effects off and sets in Cove in 19 patients. Although there is no clear evidence to avoid initiation off and sets current treatment guidelines do not recommend against and says if clinically indicated, some studies have recommended the use of acetaminophen instead of insets. However, there is no compelling evidence comparing the efficacy off both classes. Off medications There has been a general concern about the aerosolization off covert virus particles. This puts health care providers at increased exposure or increased risk of exposure to covert 19 infection. In these instances and where appropriate, we recommend the use of metered dose inhalers for nebulizer medications. In instances where nebulizer medications are required, we recommend adequate personal protective equipment for health care providers and also restricting access to patient rooms following the use off nebulizer medications. Institutional practices may very regarding the use off nebulizer medications and personal protection, and should always be verified prior to dealing or providing medications to patients. The management off covert 19 infection in geriatric patients is similar to that in the non geriatric population. The use of chronic medications is also similar in the elderly and non elderly population. However, elderly populations are more vulnerable than non elderly populations and are at increased risk for falls, delirium, depression and a sense of isolation. Poor appetite, de conditioning from reduced physical activity, functional impairment as well as dying alone. These factors should be taken into account while providing care to geriatric patients. Most off the management strategies discussed were for patients on general medical floors. In many instances, patients may show clinical decline either due to respiratory or cardiovascular or other reasons. In these instances, patients should be triaged to, ah, high level off care. And this may include respiratory care units with close monitoring, intensive care units or even transferred to a different hospital if capabilities at the current hospital cannot or are not adequate to support the patient. Despite best efforts, patients may show clinical decline on a general medical floor or in a high level off care. In all instances, patients should be closely monitored with strong ongoing communication with patients, families and caregivers. It is important to establish goals of care early in the patient's hospital stay as patients may decline rapidly, as is the case for all other patients. It's important to involve palliative care, Chaplain services were relevant and available social work and other teams to support patients, families and caregivers. The management off covert 19 patients relies on strong team based collaborative care. Our ability to screen patients for covert 19 is improving. The care of hospitalized patients varies based on institutional practices as well as availability, off PPE, availability of personnel and appropriate facilities. There is an importance to provide team based care to patients so that we can provide supportive care to patients who feel isolated. We can effectively communicate changes in clinical status toe identify only deterioration to share clinical information to minimize unnecessary exposure off healthcare providers to covert 19 patients. Coordinate care and information with specialty services. Integrate video based technology to update Corbett patients on progress off their clinical course and also update family members to alleviate anxiety and maximize support. Hospitalized patients experience an increased sense off isolation and anxiety visitor policies very based on institutional practice as well as co hurting off covert patients to dedicated covert hospital areas. It is important to maintain consistent visitor policies to minimize exposure of visitors. Toe hospital based infections minimize transmission off community infections to patients and providers practice personal protection, including the use of masks, sanitizers and physical distancing support covert patients at the end of life or with rapid functional decline. Restrict access toe wanted to family members unless granted exemption and ensure adherence to visiting hours. Discharge, planning and follow up are important aspect of care that hospitalists provide to covert patients to support hospitalists. There are many factors that can be taken into account, including discharge criteria, discharge home or to other facilities, the use of discharge checklists, discharge against medical advice, patient follow up and quarantine and care off patient caregivers. Discharge criteria are an important part off deciding when the patient it's safe for discharge from the hospital. At present, there are no studies comparing discharge criteria with post discharge outcomes. Criteria may vary based on clinical improvement, institutional protocols and technology for post discharge Follow up. Recommended criteria include absence of fever for at least 48 hours without the use of anti pirate ICS. Improvement in respiratory symptoms. Ability off the patient to safely self quarantine after being discharged from the hospital. Ability to arrange post discharge follow up discharged to a facility such as a skilled nursing facility will require adherence to that facilities guidelines and protocols prior to discharge. We recommend obtaining contact information for the patient and their caregivers. Verify ability off the patient to perform activities of daily living as well as instrumental a. D L's or that they have adequate support at home. Confirm access to equipment, access to food, access to medications for acute and chronic conditions. Provide a range, provide or arrange transportation to the patients, home or health care facility, and also educate family or caregivers on worrisome signs and symptoms. In many instances, hospitalists may be faced with patients who discharge from the hospital against medical advice. In such instances, we recommend exploring reasons for discharge against medical advice and intervening or providing support as feasible. We recommend obtaining contact information, providing resources for emergency care and reviewing institutional or local health agency policies on who should be alerted in cases off emergencies. Patient follow up and quarantine are important aspect. Off care delivered in the hospital patient follow up may include the use off Video technology to monitor or evaluate Clinical progress may include home health monitors to monitor patient's vital signs and use of supplemental oxygen and telephone follow up with patients within 48 hours after hospital discharge. Patients should be provided recommendations to quarantine at home for 14 days or for a duration based on local policies. They should be advised on when to seek care for non urgent follow up with their primary care provider or on a more urgent basis in the emergency department. Following resolution, patients could consider donating plasma for convalescent plasma programs and continue personal protection and safe public health practices. During this presentation, we reviewed several aspects for the hospitalists management off covert 19 positive patients to summarize, we reviewed anti coagulation and which has recommended. Unless pharmacologic prophylaxis is contra indicated, we recommend using a space inhibitors and ARBs for usual clinical indications. There are no recommendations against use in covert positive patients. There are no recommendations against the use of insets for usual clinical indications. Continue statins for usual clinical indications and there is no evidence to initiate or treat covert infections. Use of immune modulators should be decided on a case by case basis. Discharge criteria should include clinical improvement and ability to follow up after discharge. Institutional protocols may vary based on covitz severity and follow up capabilities. Discharge checklists should include strategies to maximize home support, including medications, nutrition and follow up with the primary care provider. Patient Follow up can be in the farm off telephone based, follow up video technology based follow up or in person with their primary care provider if required. In all instances, we recommend personal protection in public places and considering plasma donations to convalescent plasma programs. Here is a list of references and bibliography is used in this presentation. Thank you very much for your attention.
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