CME INDIA Post COVID-19 Management Protocol 2021

CME INDIA Presentation by Admin.

First Published – 16th Aug 2021. PDF link available at the end of the article.

Basic Framework By:

• Dr. Nishith Kumar, MD, FAPSR, Consultant Department of Pulmonary Medicine, OMC, Ranchi.
• Dr. Akash Kumar Singh, Internist, and Diabetologist, Spandan Multi-Specialty Hospital, Vadodara.
• Dr. Sankararaman N, DM Pulmonary Medicine Fellow at Vallabhbhai Patel Chest Institute, New Delhi.

Edited By:

• Dr. N. K. Singh, MD, FICP, Diabetologist physician, Dhanbad, Editor – cmeindia.in.

Advisor and Reviewer:

• Dr. Shashank R. Joshi, MD, DM, FICP, FACP (USA), FACE (USA), FRCP (Lon, Glsg & Edin) (Padma Shri Awardee 2014). Chair, International Diabetes Federation Southeast Asia, Past Dean, Indian College of Physicians. Member, Covid-19 State Task Force, Maharashtra.

Invitee Reviewer:

• Dr. Banshi Saboo, National President, RSSDI, Ahmedabad.
• Dr. Mangesh Tiwaskar, Consultant Physician & Diabetologist, Mumbai, Hon. General Secretary, API.

Invitee Editor:

• Dr. S. K. Gupta, MBBS MD (Med), CFM (France), Senior Consultant Physician, Max Hospital, Delhi.

Reviewer:

• Dr. Amita Nene, MD, DETRD, FCCP, Head – Dept. of Pulmonary Medicine, Bombay Hospital & Medical Research Centre, Mumbai.
• Dr. Chandrakant Tarke, MD, DNB, DM, MNAMS, EDRM, Pulmonologist, Apollo Hospital, Hyderabad.
• Dr. Murali Mohan BV, Pulmonologist, Narayana Medical Centre, Bengaluru.

Inputs:

• Dr. Anil Kumar Virmani, MD, DRM, FICP, FIACM, FACP, FDI, Consultant Physician and Cardio-Diabetologist, Jamshedpur, Jharkhand.
• Prof (Dr.) Aravinda J, MD, MRCP (London), Triple FRCP (Edinburgh, London, Glasgow) Chairman & Chief Diabetologist, Dr. Aravind’s Diabetes Center, Basaveshwarnagar Bengaluru.
• Dr. Arvind Gupta, MD, FRCP (Glasgow), FRCP (Edin), FICP, FACE, Senior Consultant and Head, Department of Diabetes, Obesity and Metabolic Disorders, Rajasthan Hospital, Opposite, Jaipuria Govt Hospital, Jaipur-302018
• Dr. Brij Mohan, Kanpur, MD, FICP, FICAM, Fellow Diabetes India, Consultant Diabetologist Physician, Kanpur.
• Dr. Prof Deepak Kumar Jumani, Senior Sexual Health physician and counselor, Asst. prof of medicine Sir JJ group of Govt Hospitals & Govt medical college, Mumbai.
• Dr. Meena Chhabra, Senior visiting consultant and diabetes specialist sir Gangaram hospital, Delhi.
• Dr. Sanjeev R. Pathak, Diabetologist, Ahmedabad.
• Dr. Noni G Singha, MD, FICP, Consultant Physician, Dibrugarh, Assam.
• Dr. Prabhat Agrawal MD (gold medalist) P g diploma of diabetes (London) MAMS, FRCP, FICP, FACP, FIACM, Professor of medicine, S N Medical college, Agra.
• Dr. Basab Ghosh, Sr Diabetologist, Agartala, Tripura.
• Dr. Th. Premchand Singh, MD, FCCP, Commonwealth Medical Fellow, UK. Retired Professor of Medicine, Regional Institute of Medical Sciences, Imphal.
• Dr. Bijay Patni, Diabetologist & Physician, Kolkata.
• Dr. Somnath, Medical Director & Chief of Medicine Diabetes Critical care, Tricolour Hospital, Hyderabad.
• Dr. B. Harish Darla, MD, DNB, MRCP(Endocrinology), MRCP(Medicine), FRCP (Edinburgh & Glasgow), Consultant Physician in Diabetes & Endocrinology, Director: Darla’s Health Care, Mysore.
• Dr. Amit Kumar, M.D. (Derm. & STD), Cosmo, Ranchi.
• Dr. Vaibhav Agnihotri, (DCH, DNB (Paediatrics), Fellowship Neonatology (IAP), PGPN, Boston, PCBD USA), Jaipur.
• Dr. Richa Agnihotri, MBBS, DGO, DNB (Obs & Gynae), FGES (lap surgeon), Jaipur.
• Special Thanks to Dr. Suresh Kumar, Infectious disease specialist, Apollo Hospital, Chennai.
• Special Thanks to Dr. B. B Rewari, MD, FRCP, Former Asso. Prof. of Medicine, Dr. RML Hospital, New Delhi. Scientist HIV/AIDS/STI/Hepatitis at WHO SEARO.

Design and Content Management:

• Mr. Rishav Manaswi, Founder (Dynamic Cognition), MBA (France), 📧 cmeindia.in@gmail.com.

Introduction (1,2)

• The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen which has resulted in both global healthcare crises and strained health resources. The pandemic has also caused morbidity and mortality at an unprecedented scale globally.

• COVID-19 is now recognized to affect multi-organs with a broad spectrum of manifestations. There are increasing reports of persistent and prolonged effects after acute COVID-19.

The post-acute COVID-19 or also called as Long COVID-19 or long haulers (among the lay public)

• It is a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms.

• It involves persistent physical, medical, and cognitive sequelae following COVID-19 infection.

• Although the number of patients recovering from COVID-19 increases significantly, the nature of post COVID-19 symptoms remains to be poorly understood which makes it even more imperative to establish an understanding of the healthcare issues surrounding the post COVID-19 infection.

• Early reports based on studies from the United States, Europe and China reporting outcomes for those who survived hospitalization for acute COVID-19, suggest that post-acute infectious consequences of COVID-19 include fatigue, dyspnea, chest pain, cognitive disturbances.  However, in the near future, the potential long-term effects from post-COVID syndrome will assume increasing importance as a surge of treated patients are discharged from the hospital, placing a burden on healthcare systems, patients’ families, and society in general. COVID-19 can result in prolonged illness, even in young adults and children without underlying chronic medical conditions.

• More research is needed to examine the long-term consequences of COVID-19 to address many unanswered questions such as:
  • What are the long-term effects of COVID-19?
  • Why symptoms persist or reoccur?
  • How these health problems affect patients?
  • What is the clinical course and likelihood of full recovery?
  • Implication of long-term health effects on return to work and daily activities?

• Understanding the biological basis of long COVID is key to identifying relevant considerations necessary for the development of multidisciplinary teams which are crucial to design strategies for preventive measures, rehabilitation techniques, clinical management, identification of those at high risk for post-acute COVID-19 and strategies with whole-patient perspectives framed to address long COVID-19 care through a coordinated management of the patients through dedicated COVID-19 clinics.

“Protective measures continue to be important in preventing COVID-19.”

Timeline of Acute Covid-19 And Post-Acute Covid-19 Phases (1,3,4)

• Acute COVID-19 usually lasts until 4 weeks from the onset of symptoms, beyond whichreplication-competentSARS-CoV-2 has not been isolated.
• Most people with COVID-19 experience mild symptoms or moderate illness. Approximately 10-15% of cases progress to severe disease, and about 5% become critically ill.
• Typically, patients recover from COVID-19 after 2 to 6 weeks.
• Post-acute COVID-19 is defined as persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. The below figure summarizes the common symptoms observed in post-acute COVID-19 syndrome.

Epidemiology (3,5)

• Globally, as per WHO statistics, as of 3 August 2021, there have been 198,778,175 confirmed cases of COVID-19, including 4,235,559 deaths. While, in India, from 3 January 2020 to 3 August 2021, there have been 31,726,507 confirmed cases of COVID-19 with 425,195 deaths, reported to WHO.

• Early reports based on studies from the United States, Europe and China reporting outcomes in subacute/ongoing symptomatic COVID-19 and chronic/post-COVID-19 syndrome for those who survived hospitalization for acute COVID-19 have now emerged on post-acute infectious consequences of COVID-19.

• An observational cohort study (hereby referred to as the post-acute COVID-19 US study) from 38 hospitals in Michigan, United States evaluated the outcomes of 1,250 patients discharged alive at 60 d by utilizing medical record abstraction and telephone surveys showed that 6.7% of patients died, while 15.1% of patients required re-admission due to post-acute COVID-19 syndrome. Of 488 patients who completed the telephone survey in this study, 32.6% of patients reported persistent symptoms, including 18.9% with new or worsened symptoms with dyspnea while walking up the stairs (22.9%) being the most commonly reported. While other symptoms included cough (15.4%) and persistent loss of taste and/or smell (13.1%).

• In a post-acute outpatient service established in Italy (hereby referred to as the post-acute COVID-19 Italian study) reported persistence of symptoms in 87.4% of 143 patients discharged from hospital who recovered from acute COVID-19 at a mean follow-up of 60 days from the onset of the first symptom. Fatigue (53.1%), dyspnea (43.4%), joint pain (27.3%) and chest pain (21.7%) were the most commonly reported symptoms, with 55% of patients continuing to experience three or more symptoms. A decline in quality of life, as measured by the EuroQol visual analog scale, was noted in 44.1% of patients in this study.

•  On April 1, 2021, The Office for National Statistics estimated that 1.1 million people in the UK were experiencing long COVID (i.e., symptoms persisting >4 weeks after the first suspected COVID-19 episode, with no alternative diagnosis). Alarmingly, an estimated 674000 people reported that their symptoms had negatively affected their ability to undertake regular day-to-day activities.

• In a prospective cohort study from Wuhan, China (hereby referred to as the post-acute COVID-19 Chinese study), long-term consequences of acute COVID-19 were evaluated by comprehensive in-person evaluation of 1,733 patients at 6 months from symptom onset. The study utilized survey questionnaires, physical examination, 6-min walk tests (6MWT) and blood tests and, in selected cases, pulmonary function tests (PFTs), high-resolution computed tomography of the chest and ultrasonography to evaluate post-acute COVID-19 end organ injury. A majority of the patients (76%) reported at least one symptom. Similar to other studies, fatigue/muscular weakness was the most commonly reported symptom (63%), followed by sleep difficulties (26%), anxiety/ depression (23%), hair loss (22%), difficulty with smell and taste (11 and 9%), trouble with mobility (7%).

• In a retrospective cohort study from USA that had analyzed the electronic health records of 236379 patients, found that 34% had psychiatric or neurological conditions in the 6 months following COVID-19 diagnosis.

• These studies provide adequate early evidence to enable the identification of people at high risk for post-acute COVID-19 syndrome. It is now understood that severity of illness during acute COVID-19 has been significantly associated with the presence or persistence of symptoms such as dyspnea, fatigue/muscular weakness and PTSD, reduction in health-related quality of life scores, pulmonary function abnormalities and radiographic abnormalities in the post-acute COVID-19 setting.

• In a Indian study (68) it was observed, 8% patients had ongoing symptomatic phase of COVID, lasting 1-3 months, and 31.8% patients had Post-COVID phase, with symptoms lasting 3-12 months. 11% patients continued to have at least one symptom even at the time of the second interview (9-12 months from the disease onset). Long-COVID was reported in almost 40% of this study group. Occurrence of Post-COVID symptoms had no correlation to age, gender, comorbidities or to the disease severity. The duration of symptom resolution was also not associated with age, gender or comorbidity but was found to be significantly associated with severity of illness at the time of admission. Fatigue was significantly more prevalent amongst the elderly patients and in those who had severe COVID-19. Persistence of breathlessness was significantly more often reported by those patients, who had severe illness at presentation. Presence of neuropsychiatric symptoms like depression, anxiety, “brain fog” and sleep disorders were reported in nearly 9% of cases. No patient reported any significant organ damage. A significant number of patients (16.5%) continued to have some form of post COVID symptoms for as long as 6-12 months, a majority of them, had resumed their routine work much earlier. 31.2% patients took 1 month to resume daily routine while 6.4% took almost 4 months to resume their daily routine. (Study represents data from follow up of Sick Patients who are likely to have more chances of post Covid symptoms.)

• However, significant amount of literature is still lacking that could shed some light on additional associations between pre-existing respiratory disease, higher body mass index, older age, sex differences and Black, Asian and minority ethnic (BAME) and dyspnea at 4–8 weeks. Therefore, major efforts are now underway to understand this long-term component also known as long COVID, post-acute sequelae of SARSCoV-2 infection (PASC), or post-COVID-19 syndrome.

Mechanisms Involved in Post-Acute Covid-19 Syndrome (6)

• An overwhelming and long-lasting counterbalancing compensatory anti-inflammatory response syndrome (CARS) that leads to post-infectious/posttraumatic immunosuppression is often seen in COVID-19 patients following trauma or a severe infection, in which a systemic inflammatory response syndrome (SIRS) SIRS is predominant. The CARS syndrome is known to dampen the proinflammatory state, prevent maladaptive multiple-organ dysfunction, and govern the return to immunologic homeostasis or normalcy.

• Multiple simultaneously interacting and opposing factors which are involved in SIRS and CARS that orchestrate a fine-tuned balance of pro- and anti-inflammatory responses ultimately determine the outcome in COVID-19.
  • Excessive inflammatory responses are a function of viral exposure or inoculum, the presence/absence of comorbidities, and the state of immunocompetence, and are characterized by excessive release of inflammatory cytokines such as interleukins and 1β, monocyte chemoattractantprotein-1, and tissue necrosis factor α collectively known as “cytokine storm” which results in the development of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), coagulopathy, hypotension, hypoperfusion, organ failure (also known as multiple-organ failure (MOF) or multiple-organ dysfunction syndrome (MODS), and death.
  • Another multifunctional cytokine, transforming growth factor beta (TGF-β) with profibrogenic, anti-inflammatory, and immunosuppressive effects that are elevated during and after sepsis as well as during and after COVID-19, is a potent inducer of fibrosis and immunosuppression, TGF-β signaling, which is mediated by Smad proteins or MAP kinases and Akt,
  • In addition to the loss of immune competence, post-COVID patients are also vulnerable to the development of post COVID pulmonary sequele, which is commonly seen in follow-up imaging of recovered patients, and which is different than Interstitial Lung Disease (IDL).

Common Lingering Symptoms of Post-Acute Covid-19 Syndrome (7-13)

• While most people with COVID-19 recover and return to normal health, some people can have symptoms that last for weeks or even months after recovery from acute illness. Even people who are not hospitalized and who have mild illness can experience persistent or late symptoms. Some patients develop medical complications that may have lasting health effects.

Till date, the most commonly reported persisting symptoms include:

Post-Covid-19 Symptoms by Organ System

• More serious long-term complications appear to be less common but have also been reported, especially in patients with severe COVID-19 who were hospitalized. The chronic complications that may persist after COVID-19 infection mainly affect the respiratory, cardiovascular, respiratory, renal and neurological systems. These have been noted to affect different organ systems in the body and include:

• Collaboration of multidisciplinary teams is necessary to provide integrated outpatient care to patients with post-acute COVID-19 syndrome in COVID-19 clinics. Depending on resources, priority may be given to those at high risk for severe post-acute COVID-19 syndrome. These categories of patients include those with severe illness during acute COVID-19 and/or requirement for care in an ICU, advanced age and the presence of comorbidities (pre-existing ARDS, obesity, diabetes, hypertension, chronic CVD, CKD, post-organ transplant or active cancer) etc.

Primary care should be given to all the patients which includes:

Summary of post-acute COVID-19 symptoms by organ system (62,63)

Timing of Follow Up (14-18)

• Patients recovering from COVID-19 range from those with mild illness not requiring medical attention to those with severe illness requiring prolonged critical care support.
• The optimal timing and location of follow-up evaluation for patients who have recovered from acute COVID-19 are unknown and depends upon several factors, including the severity of acute illness, current symptomatology, patient age, risk factors for severe illness, and resource availability.

There is no guidance on timing or location for COVID-19 follow-up after the acute illness.

Assessment (19-20)

During the initial follow-up evaluation, the following information to be gathered:

1. Patient’s acute COVID-19 illness timeline.
2. Duration.
3. Severity of symptoms.
4. Severity of complications (e.g., venous thromboembolism, presence and degree of kidney injury, supplemental oxygen requirements [including the need for noninvasive or invasive ventilation], cardiac complications, delirium).
5. COVID-19 testing results.
6. Treatment strategies followed for that patient.

General Laboratory Testing (19-20)

The need for laboratory testing in patients is determined by the severity and abnormal test results during their acute illness, and current symptoms. Most patients who have abnormal laboratory testing at the time of diagnosis improve during recovery.

For most patients recovered from mild acute COVID-19 – laboratory testing is not necessary.

Inflammatory marker

• Monitor coagulation parameters (e.g., fibrinogen, fibrinogen degradation products, activated thromboplastin time, international normalized ratio, and D-dimer levels) or inflammatory markers (e.g., erythrocyte sedimentation rate, c-reactive protein, ferritin, interleukin-6) to resolution as per need of the individual case only. (Usually not needed)

COVID-19 testing and serology

• Do not routinely re-test patients for active infection with SARS-CoV-2 at the time of follow-up outpatient evaluation.
• There is no clinical utility in obtaining SARS-CoV-2 serology (antibodies) in patients who had their acute infection documented by a positive molecular test (i.e., nucleic acid amplification test (NAAT), reverse transcriptase polymerase chain reaction [RT-PCR] test), or antigen test.
• However, for patients with prior COVID-19 based upon symptoms, but without a documented positive molecular or antigen test, the value of obtaining SARS-CoV-2 serology is unclear. Regardless, sometimes obtaining serology guides additional testing or decision-making (e.g., convalescent plasma donation, evaluation of unexplained symptoms)

Cardiopulmonary Assessment (21)

Chest Imaging (16,22-24)

• The need for chest imaging is determined by previous abnormal imaging obtained during the course of their illness as well as current symptoms.

Timing of Chest Imaging (25)

Cardiac Testing (26)

Pulmonary Function Test (16,27,28)

The optimal timing to obtain PFTs in the recovering patient is unknown.

• Pulmonary function abnormalities, may persist, particularly reduction in diffusion capacity, especially among those with more severe lung involvement.

Evaluating Exercise Capacity and Oxygenation (26)

Six-Minute Walk Test Technique (29-31)

Alternative To 6 MWT (32)

• In remote testing – patient can perform pulse oximetry after walking 40 steps on a flat surface.
• Alternatively, if on-site supervised testing – patient can perform one-minute sit to stand test (as fast as they can).
• A fall of 3% in the saturation reading on mild exertion is abnormal and indicates need for the investigations.

Management of Dyspnea

JAMA 2021; 325:1525   

Respirology 2003; 8 Suppl:S36

• Post COVID-19 dyspnea is often multifactorial (e.g., resolving pneumonia, organizing pneumonia, deconditioning, neuromuscular weakness, exacerbation of underlying lung disease, tracheal stenosis from intubation, heart failure).

Breathing Control (32)

Means using least effort and breathing gently.

• Sit in a comfortable position with your arms supported; relax and loosen your shoulders and body.
• Put one hand on chest and the other on your abdomen.
• Close your eyes – this will help you to relax and focus on your breathing.
• Slowly breathe in through your nose, with your mouth closed. Your abdomen will move out against your hand. The hand on your chest will hardly move if your breathing is controlled.
• Breathe out through your nose. This will result in your abdomen falling gently. Imagine all the tension in your body leaving as you let the air out.
• Make your breaths slow, relaxed and smooth. Try to use as little effort as possible and feel more relaxed and calmer with every breath out.
• Also, gradually try to breathe more slowly.

Breathing Techniques (32)

• Breathing control combined with any of the breathing techniques as given below
• Try all of them and follow whichever technique works well for you

1. Pursed-lip breathing

• Breathe in through your nose gently.
• Thereafter, purse your lips as if you are going to blow a candle. Blow out with your lips in this pursed position.
• Blow out only for as long as it is comfortable – do not try to force to empty your lungs.

2. Blow-as-you-go

• This helps in making tasks and activities easier.
• Use it for doing something that makes you breathless.
• Breathe in before you make the effort.
• Then breathe out while you are making the effort. For example, when standing up, breathe in before you step or stand up, and then blow out as you stand up.
• Try pursing your lips as you blow out.

3. Paced breathing

• This is useful for performing activities, like walking or climbing stairs.
• Count to yourself as you walk or move. For example, breathe in for one step and then take either one or two steps as you breathe out.
• Take more steps as you breathe in or as you breathe out, if you feel better.
• Try different combinations to find out what works best for you, e.g., two steps in, two steps out.

Management of Cough (26)

Management of Chest Discomfort/Tightness/Pain

• It does not generally require treatment unless it is interfering with the patient’s quality of life.

Known Cardiac Injury

• Patients with an established diagnosis of cardiac injury (e.g., acute myocardial infarction, cardiac arrest, atrial fibrillation) or myocarditis related to COVID-19 should be evaluated by a cardiologist.
• In addition, patients recovering from cardiac injury with resulting functional limitations (e.g., New York Heart Association [NYHA] class II or higher) should undergo cardiac rehabilitation rather than traditional physical therapy program if available, as long as there are no contraindications.

Contraindications for Cardiac Rehabilitation (33)

• Unstable angina.
• Uncontrolled hypertension – resting systolic blood pressure (SBP) >180 mmHg and/or resting diastolic BP (DBP) >110 mmHg.
• Orthostatic BP drop of >20 mmHg with symptoms.
• Significant aortic stenosis (aortic valve area < 1.0 cm2).
• Uncontrolled atrial or ventricular arrhythmias.
• Uncontrolled sinus tachycardia (>120 beats/min).
• Uncompensated heart failure.
• Third degree atrioventricular (AV) block without pacemaker.
•  Active pericarditis or myocarditis.
•  Recent embolism.
•  Acute thrombophlebitis.
•  Acute systemic illness or fever.
•  Uncontrolled diabetes mellitus.
•  Severe orthopaedic conditions that would prohibit exercise.
•  Other metabolic conditions, such as acute thyroiditis, hypokalemia, hyperkalemia, or hypovolemia (until adequately treated).

Management of Orthostasis (34)

Management of Hypercoagulability/Thrombosis

• Many patients with COVID-19 demonstrate laboratory evidence of hypercoagulability during the acute illness, and some develop venous, and arterial thromboses, especially those with severe or critical acute illness.
• Evaluate all patients for signs and symptoms of deep venous thrombosis (DVT) of the upper and lower extremities, pulmonary embolism, or arterial thrombosis (e.g., digital ischemia).
• Patients diagnosed with documented thrombosis are treated in a similar fashion to thrombosis in patients who did not have COVID-19.
• The duration of hypercoagulability in COVID-19 is unknown.
• For the majority of patients who have recovered from acute COVID-19, who were therapeutically anticoagulated for a hypercoagulable state alone, without evidence of a thrombosis, and in whom no other clear indication exists, anticoagulants are discontinued upon hospital discharge.

Management of Olfactory/Gustatory Symptoms (35-39)

• Patients experienced a loss or decrease in their sense of smell or taste with acute COVID-19, to be enquired about the degree of residual impairment, and if their appetite or weight have been affected.
• In most cases, symptoms resolve slowly over several weeks and do not require intervention except for education regarding food and home safety.

Management of Fatigue (40)

• During initial evaluation of functional impairment, determine the level of assistance needed for activities of daily living (e.g., feeding, dressing, bathing, toileting, driving, housekeeping, and grocery shopping) to inform the patient’s rehabilitation plan.
• Compare their current symptoms to their pre-illness functional status (e.g., decline in exercise tolerance, weakness, or reduced mobility).
• Screening tools used for functional assessment: 6-minute walk test, EuroQol-5D-5L, Timed Up and Go (TUG), and Short Physical Performance Battery (SPPB).

Management Of Lung Fibrosis (61)

Rehabilitation (28,41-42)

Many patients recovered from severe acute COVID-19 may require 

1. Physical and occupational therapy.
2. Pulmonary or cardiac rehabilitation.
3. Speech and swallowing therapy.

• Rehabilitation services as early as is feasible, typically within 30 days of recovery from initial infection.
• Rehabilitation programs generally last for six to eight weeks, and are followed by a clinical reassessment to determine the need for ongoing treatment.

Outpatient rehabilitation

There are a variety of available outpatient rehabilitation program.

1. In-person rehabilitation.
2. In-home rehabilitation.
3. web-based rehabilitation.

In general, in-person programs are preferred, but home or web-based rehabilitation may be appropriate for patients who cannot easily access a rehabilitation facility.

Tele-rehabilitation

• Home or web-based rehabilitation (“tele-rehabilitation”):
• Remote delivery of rehabilitation services may be preferable in areas of high infection prevalence to minimize the potential spread of COVID-19.
• Telerehabilitation can be delivered either synchronously (i.e., in real-time) or asynchronously (e.g., a prerecorded customized exercise plan).
• Telerehabilitation may be supplemented with one or more in-person visits.

Exercise prescription

• It has been postulated that graded exercise therapy is not appropriate for patients with COVID-19-related fatigue and debility given concern for worsening post-exertional malaise.
• We generally use a cautious approach to initiating a comprehensive therapy program (e.g., two to three days per week).
• Advise patients that if they feel worse (instead of better) after participation, they may need to cut back on their therapy to the previous level or stop all together.
• The development of concerning symptoms (e.g., new chest discomfort) or symptoms that are disproportionate to the degree of underlying system dysfunction may warrant additional evaluation by specialty clinicians (e.g., pulmonary, cardiac, neurology).
• Generally, start with a progressive aerobic and strength training rehabilitation program.
• Begin with breathing exercises, gentle stretching, and light muscle strengthening prior to any targeted cardiovascular program.
• Once the patient is able to tolerate light stretching and strengthening, introduce an aerobic training program.
• For aerobic training, we begin at one to three metabolic equivalents (METs) and slowly increase activity as tolerated, often over multiple sessions.

Sleep hygiene management

Yoga Practices for Prevention, Rehabilitation, and To Increase Immunity (43-51)

• Yoga practices such as Kriya, Yogasana and Pranayama have been shown to reduce airway reactivity in elderly subjects with asthma and COPD (12).
• Now sufficient evidence exists to justify testing the hypothesis that training in Yoga /Meditation can reduce susceptibility to ARI illness. Neti kriya is useful in acute coryza and symptoms of cold.

Long Haul Syndrome in Children (54-56)

The most common post-covid syndrome seen among children (<21 years) is Multisystem inflammatory syndrome in children (MIS-C). It is a condition where different body parts can become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs. The pathophysiology of MIS-C is yet unknown.

One recent study suggests that between 11 percent and 15 percent of infected youths might end up with this long-term consequence.

Many children reported with MIS-C had survived COVID-19 infection recently or had been around someone with COVID-19 infection. Even children who had mild COVID-19 infection with initial symptoms, or were asymptomatic, also had to suffer with these long-lasting effects of post-acute COVID-19 syndrome.

 MIS-C can manifest three to four weeks after asymptomatic or symptomatic COVID-19 infection and early identification is important as MIS-C can be serious, even fatal if unrecognized or left untreated among children for longer duration. However, most children who were diagnosed with this condition have gotten better with medical care.

Definition of MIS-C as per CDC

As described in the CDC Health Advisory, the definition for MIS-C among post-acute COVID-19 syndrome patients is:

• “An individual aged <21 years presenting with fever, laboratory evidence of inflammation (which includes but not limited to, one or more of the following: an elevated CRP, ESR, fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin) and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological); AND
• No alternative plausible diagnoses; AND
• Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms.”
• Note: World Health Organization (WHO) criteria for an MIS-C case definition require patients to be less than age 19 years.

Symptoms of MIS-C in Children

Management of MIS-C among children

Diagnosis

The tests performed for MIS-C include:

• Initial blood tests – CRP, ESR, CBP, CUE, Lymphopenia <1000, thrombocytopenia <150,000, neutrophilia, liver function test, kidney function test etc.
• Chest x-ray, heart ultrasound (echocardiogram), electrocardiogram, abdominal ultrasound.
• Expanded laboratory tests including pro-BNP, triglycerides, creatine kinase, amylase, blood and urine culture, hyponatremia, elevated D-dimers, prothrombin time/partial thromboplastin time (PT/PTT), INR, hsCRP, ferritin, LDH, comprehensive metabolic panel, and fibrinogen etc.
• Any other tests that may be considered necessary for diagnosis and treatment of multisystem involvement bases on patient’s signs and symptoms.
• SARS-CoV-2 detection by RT-PCR or antigen test is also indicated. In some cases, SARS-CoV-2 serologic testing is suggested, especially prior to administering intravenous immunoglobulin (IVIG) or any other exogenous antibody treatments.

Treatment

Supportive care for symptoms should be given along with ant-inflammatory agents which includes:

• Fluid resuscitation
• Ionotropic support
• Respiratory support
• In rare cases, in rare cases, extracorporeal membranous oxygenation (ECMO)
• Use of IVIG 2 grams/kg (max of 100 grams), steroid therapy (ranging from 2 to 30 mg/kg/day of methylprednisolone depending on severity of illness) and biologic therapy (e.g., anakinra, 2 to 10 mg/kg/day, subcutaneously or intravenously, divided every 6 to 12 hours) should be considered on case-by-case basis.
• Aspirin for coronary artery involvement unless there are contraindications (e.g., platelets <100,000 or active bleeding).
• Antibiotics to treat potential sepsis while waiting for bacterial cultures results
• Thrombotic prophylaxis for hypercoagulable state typically associated with MIS-C

Most children who become ill with MIS-C will need to be hospitalized and treated. Some will need to be treated in the pediatric intensive care unit (ICU). Close out-patient follow-up should be done for children including pediatric cardiology follow-up starting 2 to 3 weeks post discharge. Patients diagnosed with myocardial injury must have cardiology directed restriction and/or release for activities. Patients who receive steroid therapy or treatment with biologics should receive follow-up with the pediatric rheumatologist following discharge.

Healthcare providers should report suspected cases of MIS-C to their local, state, or territorial health departments.

Post Covid Pregnancy Related Pearls (58,59,60)

• During pregnancy it is most common to experience profound changes to how the body functions, which includes making it more susceptible to some infectious diseases – one important change is a slight suppression of the immune system.
• This high-risk group has been initially overlooked due to limitations of available data. However, much attention is now given to this patient group as it is observed that post-acute COVID-19 symptoms lingered in many of the pregnant women who recently survived the infection irrespective of severity of the infection or being asymptomatic.
• However, according to the available data, the symptoms among pregnant women manifested differently compared to those reported in non-pregnant population. The symptoms continued to persist eight weeks after becoming sick. The median length of symptoms was 37 days. For example: fever was uncommon in some women even though it has been a hallmark sign of this disease; it was an initial symptom in just 12 percent of the pregnant individuals and present only in 5 percent after one week of illness. Other signs of COVID-19 including cough, loss of smell, fatigue, and shortness of breath persisted in most of the women for up to two months – according to PRIORITY study published on October 7 in Obstetrics & Gynecology by Jacoby from University of California.
• Long-term effects on fetal development and child health also remains a major concern and an issue where extensive research is warranted. It is important to understand the perinatal outcomes that may arise during fetal organogenesis.
• Pregnant women with post-acute COVID-19 syndrome needs to be given additional support for symptomatic treatment and regular out-patient follow-up, regular fetal growth scans and well-being scans etc. as they are at increased risk for preterm birth (delivering the baby earlier than 37 weeks) and might be at increased risk for other poor outcomes related to pregnancy such as pregnancy loss etc.
• It is of utmost importance that the clinician differentiates the symptoms of long haulers from post-natal depression as long haulers can mimic postpartum depression like picture. Thus, their symptoms should not be ignored and taken as a challenge so that the mothers do not become silent sufferers.

Post COVID-19 Diabetes (61-62)

• Both, new-onset hyperglycemia and new-onset diabetes (both T1DM and T2DM) have been increasingly recognized in the context of COVID-19.
• No conclusive evidence yet suggests direct tropism of SARS-CoV-2 on the β cells of pancreatic islets. (61)

1. New onset diabetes in Covid has been seen and possible mechanisms are as follows:
   • Covid virus gains entry into cells via ACE 2receptors- ACE 2 expression in islet cells and the exocrine cells are inconsistent but seen. Pm studies have shown that beta cells were infected with the virus.
   • In vitro studies reveal that the ACE 2 receptors is expressed on beta cells with co factors TMPRSS2, NRP1 &TRFC.
   • Infection with Covid causes selective beta cells apoptosis and also causes beta cells trans differentiation.
2. An increased risk associated with development of new-onset diabetes following hospitalization has been found.
3. Definitive conclusion cannot be reached about link between COVID-19 and Type 1. The prevalence of T1DM in patients with COVID-19 19 ranged from 0.15% to 28.95% and most presented with DKA. Direct correlation is not established. To establish a link, we need more robust evidence and well-designed epidemiological studies.
4. Immunological destruction of beta cells by any viral infection including COVID-19 can trigger development of Type 1 DM, particularly in those who are predisposed.
5. Most patients who had mild COVID-19 and were found to be diabetes post COVID-19 usually reverted back to normoglycemia in 3-6 months.
6. 3 scenarios are possible:
   • Undiagnosed type 2 diabetes in a patient who was not aware he had diabetes and was tested and diagnosed as diabetes.
   • Person had IFG /IGT and the acute inflammation/steroid treatment led to progression to type 2 Diabetes.
   • Person was at a high risk genetically and had risk factors like overweight /obesity and sedentary lifestyle, Covid led to increase in insulin resistance and beta cells could not cope with it and patient developed diabetes.
7. Details of management has been given in CME INDIA management Protocol

All approved oral antidiabetic agents appear to be safe in people with T2DM having COVID-19.

At present no conclusive data are available to indicate a mortality benefit with any class of oral hypoglycemic drugs.

Post Covid Dermatological Manifestations

Hair loss is the predominant symptom, observed in approximately 20-30% of patients.

• Telogen effluvium (TE), first described by Kligman in 1961, is a diffuse, nonscarring shedding of hairs, resulting from the early entry of the hair into the telogen phase
• Classic TE is self-limited and acute, defined as lasting less than 6 months, and occurs approximately 3–4 months after a triggering event
• Moreover, a chronic form of TE is reported, exceeding 6 months of duration.
• Several agents have been associated with TE, including drugs, physiological stress (surgery and high fever), emotional stress, chronic infections, dietary and iron deficiency, and smoking.
• TE following COVID infection is seen earlier than classical TE, usually presenting between 1-3 months after the infection.
• The patients present with increased shedding of hairs in bunch, along with the hair loss the hairs become dry and brittle also in many cases.
• Women are more frequently involved as compared to males, and all age groups are affected.
• Post-COVID TE is having a profound effect on the quality of life of the affected individuals.
• Common pathogenetic mechanisms occurring in COVID-19 TE may be hypothesized:
  • Acute TE may be induced by the intense release of pro-inflammatory cytokines as a consequence of viral infections. o Recombinant interferon alpha-2b therapy has similarly been reported to induce TE.
  • High levels of IL-6 act on the hair follicle (HF), inducing the catagen phase as well as causing local inflammation and collapse of the immune privilege. o High levels of IL-4, which are typical of COVID-19 in the elderly, also determine keratinocyte apoptosis in HF.
  • Additional molecules showing high levels in COVID-19 are metalloproteinases 1 and 3 and IL-1β, which may inhibit the HF growth.
• TE can be diagnosed by clinical examination aided by trichoscopy and trichogram.
• Counselling is of paramount importance to abate the psychological stress of the patients.
• Proper diet, healthy lifestyle, stress reduction should be emphasized upon.
• Treatment consists of vitamin supplementation containing alpha-lipoic acid, calcium pantothenate, vitamin D3, biotin, iron daily. Also use of some hair serums containing procapil or capixyl will help in the management.
• Clinicians should be aware of this entity as it is being encountered very frequently.
• Other dermatological manifestations include urticaria, maculopapular rash, pityriasis rosea, pruritus, purpuric lesions.
• These conditions can be treated with use of oral anti-histamines, topical steroids, moisturizers and most importantly counselling of the patient.
• There can be cutaneous adverse reactions to the drugs used in COVID management. A delayed type hypersensitivity reaction to heat killed Mycobacterium W (Sepsivac), presenting as papule or nodule and in some cases even ulceration have been reported. These usually heals over several months leaving behind small scars.

Post-Covid Sexual Issues (67)

Covid-19 is a Endothelial Dysfunction.

Covid-19 today has been proven to be a generalised endothelial disease, In the beginning its an infection with the virus like a cold, and then the body reacts to it, it’s the inflammatory response of the host. This response may, in some victims, go too far and disturb vasomotion, resulting in tissue ischemia und pulmonary hypertension, activating tissue factor and coagulation, and increasing endothelial permeability. It also can and does cause oedema in the lungs and other organs, and as such is responsible for the cardiovascular complications that results in so many deaths.

All these lead to reduced eNOS and reduction in NO and EPC functions.

Penile arteries are the smallest arteries and as the inflammatory response is generalised the penile arteries are the first to be affected. Hence Covid-19 infection leads to endothelial dysfunction and erectile dysfunction. Also in patients who already have co morbid conditions like Diabetes, hypertension, dyslipidaemia obesity they already have endothelial dysfunction so in them erectile dysfunction has to co-exist if they get Covid -19 infection and as we all know erectile dysfunction is a sentinel marker of coronary artery disease, these patients with co morbid conditions and getting covid will always have high mortality.

In younger individuals because of Covid-19, which is a endothelial disease also reduces the blood supply to reproductive organs and reduction in testosterone and hence reducing libido and also spermatogenesis.  So the passport to immunity with COVID -19 is mandatory for all elderly men with high risk of vulnerability of getting CAD. This could be achieved with covid appropriate behaviour, getting vaccinated as soon as possible, PDE5 inhibitors have been proven to be therapeutic specially in patients who have CVD, diabetes and heart disease.

• COVID-19 increases the risk of developing erectile dysfunction (ED) by nearly six times Post COVID.
• There seems to be no definite evidence of the presence of SARS-CoV-2 in seminal fluid however, there is reason to suspect that sexual quality of life and function might also be impaired as a consequence of COVID-19.
• Few studies are highly suggestive of the role of the infection in the development of the sexual dysfunction and of the possible clinical relevance of COVID-19 as an additional risk factor for the development of ED.
• The bidirectional interaction between sexual activity and psychological well-being,the removal of the possible influence of anxiety and depression confirmed that the increased prevalence of ED here found is not only a consequence of the psychological burden, but also prominently due to other, bona fide organic factors.
•  Sexual activity is closely associated with mental and psychological health; it is, therefore, unsurprising that sexual desire and frequency have declined in both genders.
• The importance of investigating the possible causes of ED becomes of paramount importance. Identifying and treating potential comorbidities would have potentially beneficial effects on erectile function.
• COVID-19 survivors might develop sexual and reproductive health issues. Andrological assessment and tailored treatments should be considered in the follow-up.
• Testicular damage in COVID-19 might induce a state of hypogonadism as proven by decreased testosterone-to-LH ratio in patients with COVID-19, suggestive of impaired steroidogenesis resulting from subclinical testicular dysfunction.
• Independently of whether testosterone is a friend or foe for COVID-19, it should be acknowledged that the testis is a target for SARS-CoV-2 and the possibility for long-lasting consequences on the endocrine function exists, even for recovered patients.
• Phosphodiesterase-5 (PDE-5) belongs to the PDE superfamily of enzymes, the last step of the NO/cGMP/PDE pathway and is one of the key elements in drug treatment of ED.
• There is quite enough reason to suspect that male sexual and reproductive health could be affected in the survivors, by the sequelae of the COVID-19, both in the short and long terms
• Erectile function, as a surrogate marker of cardiovascular/pulmonary health, could also become extremely valuable as a quick and inexpensive first-line assessment of the pulmonary and cardiovascular complications for COVID-19 survivors.
• Diagnostic procedures, such as penile color-doppler ultrasound and hypothalamic-pituitary–testicular axis evaluation will be necessary to assess the extent to which COVID-19 has been able to impair erectile function.
• Tailored psychological interventions would be necessary to adequately support patients who develop sexual dysfunction consequently to the containment measures.

Key Points

• COVID-19 infection may probably play the same role of an immune triggers in other autoimmune diseases. Therefore, patients should be tested for antinuclear antibodies and the tests must be repeated over time after 6 weeks, especially if the patients are young women with rheumatologic pain to rule out a possible dormant underlying autoimmune disease.
• Patients with persistent symptoms (beyond 8 weeks after the onset of COVID-19) should go for a first evaluation, including biological tests withCOVID-19 serology, antinuclear antibodies and transthoracic echocardiography to rule out other diagnosis, especially myopericarditis, with a chest computed tomographic scan to assess if there are any sequelae of COVID-19.
• In case of persistent symptoms beyond 3 months, a thorough investigation should be performed to assess the possible relationship between those chronic inflammatory symptoms and COVID-19.
• Treatment and management of post-acute COVID-19 symptoms often requires multidisciplinary teamwork with other specialists, including a psychologist, a pulmonologist, a neurologist and a specialist in physical medicine and rehabilitation.
• Thereafter, a better understanding of COVID-19 might help the healthcare professionals to design and propose an adequate therapeutic and management strategies that depends on the acknowledged physiopathology of the disease.

“Protective measures continue to be important in preventing COVID-19”

Suggested Useful Link

Post COVID 19 – Oxford Health NHS Foundation Trust

Supplementary Tables

Investigations (Not all patients need it)

Dealing with important symptoms

Lung Fibrosis

References

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