Algorithms for adult outpatient care of coronavirus disease 2019 (COVID-19) and its assumption

The paper presents algorithms for adult outpatient care of coronavirus disease 2019 (COVID-19) and its assumption.

The pandemic of a novel coronavirus disease, the germ of which was officially named severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the disease itself -Coronavirus disease 2019  [1], changed the life of all mankind. It challenged medical workers to rapidly diagnose and manage COVID-19 patients in conditions, where data on the epidemiology, clinical features, prevention and treatment of a novel disease was extremely limited, and often completely absent.
In this emergency, the Russian healthcare system was able to mobilize in a timely manner and refocus on the fight against COVID-19. Interim guidelines have played and continue to play a huge role at present, aimed at combining and the fastest spread of best experience in the prevention, diagnosis and treatment of COVID-19. Already on January 29, 2020, the Ministry of Health of the Russian Federation released the first version of the interim guidelines on prevention, diagnosis and treatment of .
This part includes a diagnostic screening scheme for suspected, probable (clinically confirmed) and confirmed COVID-19 cases. The algorithm draws the doctors' attention to the fact that laboratory tests for SARS-CoV-2 RNA should be carried out for all persons with ARI manifestations. In case of a negative test by immunochromatography or other immunochemical methods, it is recommended to use nucleic acid amplification techniques. In a mandatory manner, such an examination must be performed in following cases: persons who arrived to Russia with ARI symptoms or when they appear during the medical observation; those who have been in contact with a COVID-19 patient, if there are symptoms that do not rule out COVID-19, as well as in the absence of clinical manifestations -on the 8-10 th day of medical follow-up after the day of contact with a COVID-19 patient; those with communityacquired pneumonia; those aged >65 years who seek medical attention with respiratory symptoms.
The algorithm includes a table for the interpretation of laboratory test results, developed for the 10 th version of guidelines, which, being simple and intuitive, is of great value for practical use.
The main clinical characteristics, types and manifestations of COVID-19 are highlighted in separate blocks of the algorithm for primary care practitioners. Given the disease peculiarities with an atypical mild performance without fever and cough in elderly and senile patients, which do not correspond to the severity of disease and prognosis, but at the same time often accompanied by delirium, the algorithm includes the Richmond Agitation-Sedation Scale (RASS).
The second part of algorithm provides action options for outpatient medical workers on managing patients with ARI, in particular -those contacted with a COVID-19 patient, as well as low-and high-risk patients with mild, moderate and severe ARI.
The approaches to management of patients at home are considered. The physicians' attention was drawn to necessarity to inform a patient about the need to call a doctor or an ambulance team in case of condition deterioration, as well as about possible ways to seek medical help. Persons living with a patient in the same room should be informed about the risks of COVID-19 and the need to temporarily reside elsewhere.
Interim guidelines contain detailed information for all healthcare levels for patients with COVID-19outpatient, inpatient, rehabilitation and prevention. At the same time, this format of guidelines somewhat limits their immediate use in outpatient practice.
In this respect, on the initiative of the Omsk Oblast Ministry of Health and the Omsk State Medical University, with the active participation of National Medical Research Center, a working group and an expert committee were created, the purpose of which was to develop an algorithm for adult outpatient care of COVID-19 and its assumption, with regular updating based on the current interim guidelines on prevention, diagnosis and treatment of COVID-19 and the order of the Ministry of Health of Russia dated March 19, 2020 № 198n. One of the important tasks of working group was to format the algorithms in compact manner, convenient to visual perception (Appendix 1).
Core of the working group was made up of teaching staff of the clinical profile, chief external expert of various levels and health professionals, as well as the expert committee -the heads of outpatient and inpatient medical organizations, researchers, and workers of regional and practical healthcare system.
Currently, algorithms (version 5) have been prepared and updated, based on version 11 of the interim guidelines on prevention, diagnosis and treatment of COVID-19 and the order of the Russian Ministry of Health dated March 19, 2020 № 198n.
The first part of algorithm is devoted to COVID-19 diagnosis. The algorithm begins with a table for classifying COVID-19 by severity. Taking into account the empirically changing approach to x-ray imaging (primarily computed tomography, CT) for diagnostics, to optimize the work of primary care physicians, this part includes a block of CT criteria for involvement extent and indications for CT scanning. In addition, the attention of doctors is focused on the fact that imaging data do not replace the results of tests for SARS-CoV-2 ribonucleic acid (RNA). The absence of CT changes does not rule out the COVID-19 and pneumonia risk after the analysis. In the absence materials on caring COVID-19 patients, and general recommendations for protection against airborne diseases. If a decision is made on the further provision of outpatient care to a patient, informed consent on provision of outpatient healthcare and compliance with the isolation regime must be signed.
In the same section of the algorithm, the criteria for outpatient monitoring are given. Particular attention of doctors is focused on episodes of a repeated increase in body temperature after its normalization for ≥1 day, on respiratory rate values and the indications for hospitalization of COVID-19 outpatients.
The third section is devoted to outpatient drug prevention, depending on the clinical situation and therapy regimens for COVID-19 outpatients with mild and moderate course. It is important to note that the algorithm ref lects the fundamental changes in drug therapy that appeared in the 11 th version of guidelines, the most important of which is the final exclusion of hydroxychloroquine from the recommended therapy.
This made it possible to significantly optimize and simplify a number of aspects of outpatient management of patients, since there was no need to predict and monitor the cardiotoxic effects of chloroquine. With hydroxychloroquine therapy, all patients were required to additionally perform electrocardiography (ECG) before starting treatment, as well as every 5 days with an assessment of QT interval. To control cardiotoxicity, it was necessary to perform an ECG on the 3 rd day of therapy, 2-3 hours after taking the drug. All outpatients were required to closely monitor their symptoms, paying attention to risk factors (RFs) for arrhythmias (syncope, dehydration, new medications). When arrhythmia RFs were detected, an unscheduled ECG was required. With outpatient hydroxychloroquine therapy under quarantine conditions and limited resources, it was also necessary to assess the risk of drug-induced QT interval prolongation using the Tisdale Risk Score and identify additional RFs for QT prolongation using a modified checklist.
In the same section, the attention of doctors is drawn to three issues when organizing outpatient care for COVID-19 patients. These are the features of antibiotic, corticosteroid and symptomatic therapy.
The final section of the algorithm describes the out patient monitoring of patients with COVID-19. In particular, it is indicated that patients discharged after prolonged mechanical ventilation and/or with significant functional/organic disorders requires remote counseling and then follow-up visit to office 4 and 8 weeks after discharge, respectively. In the absence of complaints and pathological changes in such patients, further outpatient monitoring should be carried out in accordance with the order of the Russian Ministry of Health dated March 29, 2019 № 173n. If lung CT reveals signs of pulmonary fibrosis, interstitial lung disease, vasculitis, a patient should be referred to pulmonologist. Patients without such abnormalities but with complaints or changes according to other studies require differential diagnosis with other diseases/conditions. Patients with prior mild or moderate pneumonia who was not managed in the intensive care unit (ICU), including those treated on an outpatient basis, should be followed up in accordance with the order of the Russian Ministry of Health dated March 29, 2019 № 173n, with the determination of blood oxygen saturation and a chest x-ray.
The doctors' attention is focused on the fact that during the outpatient monitoring of patients after COVID-19, it is necessary to assess psychosocial RFs, including anxiety and depression symptoms, with the treatment of the identified abnormalities, as well as with the involvement of a psychologist, psychiatrist, social workers.
Monitoring of practical application of preliminary algorithm versions, carried out by a committee of experts and a working group in the outpatient medical organizations of Omsk Oblast, showed good applicability and convenience in the outpatient service. This made it possible, starting from 3 rd version, to use all subsequent updated revisions in the work of therapeutic service of the Russian Ministry of Health.
The authors hope that further application of the algorithm will be useful for outpatient health care professionals in Russia. Indications for CT: primary assessment of thoracic organs in patients with severe disease progressive; differential diagnosis of identified changes; triage and dynamic assessment in case of moderate, severe and very severe disease course.

Outpatient diagnostic screening
Clinical manifestations of AVI: t >37,5 ○ C, + one or more of the following features: cough (dry/scanty sputum); dyspnea; chest congestion; SpO 2 ≤95%; sore throat; nasal congestion or mild rhinorrhea; loss of smell and/ or taste; conjunctivitis; weakness; muscle pain; headache; vomiting; diarrhea; skin rash in the absence of other known causes of it, regardless of the epidemiological history 1. ARI clinical performance (see) + one or more of the following signs: return from a foreign trip 14 days before the onset; close contacts in the past 14 days with a person followed up for COVID-19, who subsequently fell ill or who had a laboratory confirmed COVID-19; having professional contacts with individuals with a suspected or confirmed COVID-19 Laboratory test for SARS-CoV-2 RNA should be carried out for all persons with ARI signs. The main type of biomaterial for laboratory research is oropharyngeal and nasopharyngeal swabs. In case of a negative test for SARS-CoV-2 antigen by immunochromatography or other immunochemical methods, the determination of SARS-CoV-2 RNA using nucleic acid amplification is recommended. The detection of anti-SARS-CoV-2 IgA, IgM and IgG antibodies is also used.
In a mandatory manner, such an examination must be performed in following cases: persons who arrived to Russia with ARI symptoms or when they appear during the medical observation; those who have been in contact with a COVID-19 patient, if there are symptoms that do not rule out COVID-19, as well as in the absence of clinical manifestations -on the 8-10 th day of medical follow-up after the day of contact with a COVID-19 patient; those with community-acquired pneumonia; those aged >65 years who seek medical attention with respiratory symptoms. For workers of medical organizations who have a professional risk of infection, before the appearance of IgG, a laboratory test for SARS-CoV-2 RNA should be carried out 1 time a week; if symptoms do not rule out COVID-19 -immediately.

Clinical manifestations in elderly and senile patients
In elderly patients, an atypical performance without fever and cough may be observed due to reduced reactivity.
COVID-19 symptoms may be mild and not consistent with the severity of disease and prognosis.
Atypical symptoms of COVID-19 in elderly and senile patients include delirium.
Brief confusion assessment score (identification of delirium in elderly and senile patients) ≥2 errors → step 3

STEP 3. Assessment of level of consciousness changes
The Richmond Agitation-Sedation Scale (RASS): +4 COMBATIVE: belligerent, aggressive, dangerous to others (urgently inform the doctor about these phenomena); +3 VERY AGITATION: pulls on or removes tube(s) or catheter(s) or has aggressive behavior (inform doctor); +2 AGIATED: Frequent no purposeful movement or patient-ventilator desynchrony; +1 RESTLESS: anxious or apprehensive but movements not aggressive or vigorous; 0 ALERT AND CALM ; -1 DROWSY: not fully alert, but has sustained (more than 10 seconds) awakening, with eye contact, to voice; -2 LIGHT SEDATION: briefly (less than 10 seconds) awakens with eye contact to voice; -3 MODERATE SEDATION: Any movement (but no eye contact) to voice RASS* is not 0 → DELIRIUM; RASS* = 0 → step 4

STEP 4. Assessment of impaired consciousness
Assessment: 1. Will the stone float on the water? 2. Does the fish live in the sea? 3. Does one kilogram weigh more than two? 4. is it possible to hammer a nail with a hammer? Command: "Show this number of fingers" (show 2 fingers) "Now do the same with the other hand" (do not show) OR "Add another finger" (if the patient cannot move both hands) ≥2 errors → DELIRIUM; 0-1 error → NO DELIRIUM

Options for actions of medical workers in outpatients with ARI
There was contact with a COVID-19 patient.
No ARI symptoms ARI mild in a patient not at risk. Presence of 2 criteria: SpO 2 ≥95% (mandatory criterion); t <38 ○ C; RR ≤22 Mild ARI in high-risk patient*.
Presence of 2 criteria: SpO 2 ≥95% (mandatory criterion); t <38 ○ C; RR ≤22 Moderate or severe ARI. Presence of 2 criteria: SpO 2 <95% (mandatory criterion); t ≥38 ○ C; RR >22; CT score 2 (>25%) TREATMENT AT HOME: Medical care for a patient with a positive test result for COVID-19 can be provided at home in the absence of clinical manifestations of a mild disease course (t <38,0 ○ C, RR ≤22 per minute, SpO 2 ≥93%), as well as in case of moderate course in adults in the presence of conditions (the possibility of self-isolation, no persons living with the patient >65 years old, etc.). A patient should be informed by a medical professional about the need to call a doctor or an ambulance team in case of deterioration (body t >38,5 ○ C for 3 days or more, shortness of breath, SpO 2 <93%), as well as possible ways to seek medical help. Persons living with the patient in same room should be informed about the risks of COVID-19 and the need to temporarily reside elsewhere. A patient and persons living with him should be informed that a violation of sanitary and epidemiological rules, which entailed an infection spread, may lead to their prosecution. If a decision is made on the further provision of outpatient care, informed consent on provision of outpatient healthcare and compliance with the isolation regime must be signed.
OUTPATIENT MONITORING. Body temperature monitoring (daily at least 2 times a day in the morning and evening); particular attention should be focused on episodes of a repeated increase in body temperature after its normalization for ≥1 day. RR monitoring is assessed daily; in case of an increase in RR, it is necessary to focus not only on its standard normal values, but also on the increase in comparison with the initial ones. When signs of respiratory failure develop or worsen, SpO 2 should be carefully monitored. In case of RR ≥22 per min during treatment at home, it is necessary to consider hospitalization of a patient.
A patient with a positive test for COVID-19 should be hospitalized: with moderate, severe and very severe coarse (severity criteria are in the table "Severity of COVID-19"); in case of maintaining t ≥38,0 ○ C during the outpatient treatment for ≥3 days; regardless of temperature, in the presence of RR ≥22 per min and/or SpO 2 <93%; with a mild disease course, if the patient's age is >65 years or there are symptoms of ARI in combination with HF, diabetes, respiratory diseases (asthma, COPD); in case of living with risk-group persons (>65 years old; persons with chronic respiratory, cardiovascular, endocrine diseases, as well as systemic connective tissue diseases, chronic kidney disease, cancer, immunodeficiencies, motor neuron diseases, liver cirrhosis, chronic inflammatory bowel diseases) and the impossibility of their resettlement, regardless of disease severity in a patient; with a mild disease course in children who have ARI symptoms in combination with following chronic diseases: heart failure, diabetes, asthma, congenital heart and lung diseases, those receiving immunosuppressive therapy, and others; living with risk-group persons.
The following patients should be hospitalized, regardless of severity: patients at risk (age >65 years in combination with following disorders: hypertension; HF; cancer; hypercoagulation; disseminated intravascular coagulation; ACS; diabetes; motor neuron disease; liver cirrhosis; long-term intake of GC and biological therapy for inflammatory bowel disease; rheumatoid arthritis; patients receiving hemodialysis or peritoneal dialysis; patients with immunodeficiencies, including those with HIV infection without antiretroviral therapy; receiving chemotherapy); patients living in a hostel, a crowded apartment, with persons >65 years old, with persons suffering from chronic respiratory, cardiovascular and endocrine diseases.
Fourteen-day home isolation with a certificate of incapacity for work. When symptoms of ARI appear, calling a doctor at home. Taking a control nasoand oropharyngeal swabs on the day of reference with the initial examination by a doctor (as soon as possible); if ARI symptoms appear -immediately! Naso-and oropharyngeal swabs on the day of reference, with an initial examination by a doctor. Fourteen-day home isolation with a certificate of incapacity for work. Daily audio monitoring of the patient state. Repeated visit to office in case of deterioration. Taking a control naso-and oropharyngeal swabs (from 10 to 14 days twice -in a confirmed COVID-19 case) Hospitalization by a specialized ambulance team

*Home health care is allowed for adult patients with a moderate COVID-19 in the presence of conditions
Outpatient medication prophylaxis, depending on the clinical situation

CORTICOSTEROIDS (methylprednisolone, dexamethasone) are indicated only in cytokine storm! It is not recommended to use GCs for the treatment of patients with mild to moderate COVID-19 severity, including on an outpatient basis.
Early predictors of cytokine storm: increased serum CRP >46 mg/l, ferritin >250 ng/ml; lymphopenia (<10%) and/or increased ALT >60 U/L, and/or AST >87 U/L, and/or LDH >416 U/L, and/or D-dimer level (by 4 times or more compared to the reference value) or its rapid increase, and/or the troponin I >1,09 ng/ml. There are following laboratory signs of a cytokine storm: leukopenia, a decrease in the number of monocytes, eosinophils and basophils, T-and B-lymphocytes, an increase in the serum interleukin-6 (>40 pg/ml), an increase in fibrin degradation products level, hyperfibrinogenemia, normal or decreased prothrombin and activated partial thromboplastin time, normal antithrombin III level. SYMPTOMATIC THERAPY includes: relief of fever (antipyretic drugs such as paracetamol); complex therapy of rhinitis and/or rhinopharyngitis; complex therapy of bronchitis (mucoactive, bronchodilator and other drugs). Antipyretics are prescribed at t >38,0-38,5 ○ C. With poor tolerance of fever, headache, increased blood pressure and severe tachycardia (especially in the presence of ischemia or arrhythmias), antipyretic drugs are also used at lower body temperature. The safest drug is paracetamol. For the local treatment of rhinitis, pharyngitis, with nasal congestion and/or nasal discharge, agents based on saltwater should be considered (isotonic, and with congestion -hypertonic). If it is ineffective, nasal decongestants are indicated. In case of ineffectiveness or severe symptoms, various antiseptic solutions can be used.

Outpatient monitoring in COVID-19 patients
Patients discharged after long-term mechanical ventilation, and/or with significant functional/organic disorders: 4 weeks after discharge: remote counseling (assessment of the general condition, detection of depression, symptoms of suspected thromboembolism, other syndromes and diseases); 8 weeks after discharge: visit to office, with following investigations (according to indications): chest x-ray; spirography; oxygen saturation at rest and during exercise (6-minute walk test is possible with determination of oxygen saturation before and after the test); echocardiography (other tests if indicated). In the absence of complaints and pathological changes -outpatient monitoring in accordance with the order of the Russian Ministry of Health dated March 29, 2019 № 173n is indicated. If lung CT reveals signs of pulmonary fibrosis, interstitial lung disease, vasculitis, a patient should be referred to pulmonologist. Patients without such abnormalities but with complaints or changes according to other studies require differential diagnosis with other diseases/conditions. Patients with prior mild or moderate pneumonia who was not managed in the intensive care unit, including those treated on an outpatient basis, should be followed up in accordance with the order of the Russian Ministry of Health dated March 29, 2019 № 173n, with the determination of blood oxygen saturation and a chest x-ray. If there is a suspected cancer was revealed during inpatient treatment, repeated chest x-ray 6 weeks after discharge is indicated (if necessary -lung CT and oncologist consultation).
Patients with persistent lung X-ray or CT abnormalities after discharge from the hospital require lung X-ray of CT 8 weeks after the last scan. When pathological changes are detected, the following investigation should be performed: spirography; blood oxygen saturation at rest and during exercise (including a 6-minute walk test); echocardiography. If pulmonary embolism is suspected, immediate CT pulmonary angiography. If pulmonary fibrosis or interstitial lung disease is suspected, high-resolution CT should be performed. If lung CT reveals signs of interstitial lung diseases, pulmonary vasculitis, pulmonary hypertension, a patient should be referred to pulmonologist and/or cardiologist. In the absence of such abnormalities, but the presence of complaints (or changes according to other investigations), a differential diagnosis with other diseases should be carried out.
During the outpatient monitoring, it is necessary to assess psychosocial RFs, including anxiety and depression symptoms, with the treatment of the identified abnormalities, as well as with the involvement of a psychologist, psychiatrist, social workers. All patients should be informed that in case of progressing or developing new respiratory symptoms before the scheduled examination, they should immediately seek medical attention.