COVID-19 in children Dr. Asaduzzaman , Resident, Phase A, Neonatology & Dr. Habibur Rahman Bhuiyan , Resident Phase a, Neonatology
This is a universal crisis and, for some children, the impact will be lifelong.
Quietness of the Earth due to COVID 12
COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare
HISTORY Coronaviruses(CoV) were first identified as a cause of the Considered relatively non fatal until 2002, then⦠SARS-CoV outbreak in2002ā03 from Guangdong province of China resulted in 8098 confirmed cases ,killing 774 people MERS-CoV outbreak in2012 from Middle-East caused 2494 cases with 858 deaths Current outbreak with a novel strain is still ongoing!
The virus Belongs to the Corona viridae family Corona viruses are 120-160nm sized particles Single stranded ,(+) ve sense, non-segmented RNA Viral envelope has numerous petal/club-shaped glycoprotein spikes resembling crown-like projectionsāfor which named Coronavirus Helical nucleocapsid symmetry Sensitive to heat,drying,PH and lipid solvents
VIRAL PROTEINS M glycoprotein (E1 protein): Determine budding site S (spike) glycoprotein (E2 protein): Binds to specific receptor N glycoprotein Binds to viral RNA HE ( Haemaglutininesterase glycoprotein)
VIRAL RECEPTOR SARS CoV-2 binds to human angiotensin converting enzyme(ACE)2.
Viral replication
REPLICATION Occurs in cell cytoplasm. Attachment of the viral S protein to host receptors mediates endocytosis of virus into the cell Virus membrane fuses with endosomal membrane and the ssRNA (+) is released in to the cytoplasm Synthesis and proteolytic cleavage of the replicase polyprotein Replication occurs in viral factories. A dsRNA genome is synthesized from the genomic ssRNA (+).
REPLICATION CONT⦠. The dsRNA genome is transcribed providing viral mRNAs/new ssRNA (+)genomes Synthesis of structural proteins encoded by sub genomic mRNAs. Assembly and budding at membranes of the endoplasmic reticulum(ER),the intermediate compartments,and /or the Golgi complex. Release of new virions by exocytosis.
MODE OF TRANSMISSION Coughing and sneezing without covering the mouth disperse virus-containing droplets into the air Touching or shaking hands can pass the virus from one person to another Contact with a contaminated surface or object and then touching nose,eyes,or mouth
Incubation period 3 to 7 days (median 5.1 days) up to 2 weeks as the longest time from infection to symptoms Novel epidemic doubled about every seven days. Basic reproduction number (R0 - R naught) is 2.2. In other words, on average, each patient transmits the infection to an additional 2.2 individuals.
In China : 2.2 % aged <19 years In the UK : 2 % aged < 18 years In the USA : 2 % aged <18years. In Italy: 2.1 % aged < 18 years. In Spain: 0.8% aged < 18 years. In Bangladesh: 3% aged < 10 years 7% aged 11-20 years Global Scenario of Paediatric COVID 19
Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study, Lancet Infectious Disease, April 27thĀ 2020,Ā https://doi.org/10.1016/S1473-3099(20)30287-5 This was a fairly impressive study looking at contact tracing of 1286 contacts of 391 patients with COVID-19. Only 20 (5.1%) of the initial 391 cases were children, of which 2/3 were asymptomatic. They discovered a secondary attack rate of 15% for household contacts and 9.6% overall. The most important finding is that the rate of infection in children <10 years (7.4%) was similar to the population average (7.9%). The findings of this study suggested that children were becoming infected at a similar rate to adults but were much less likely to be asymptomatic. As no repeat testing was performed, it is unclear if these children were truly asymptomatic, or presymptomatic . Subsequent studies have consistently shown lower attack rates in children, and the reason for this discrepancy is unknown
small number of other studies of transmission within a school setting, so far, Demonstrated infrequent transmission from children. No case of onward transmission to other children or adults within the school occurred. In the case of children, no onward transmission was detected at all .
Some children in England will be going back to school from Monday 1 June. Children are at extremely low risk of becoming ill from the virus Across the UK, 0.01% of deaths were people under 15, 1% were aged 15-44 and about 75% were over 75. Children have so far only accounted for between 1% and 5% of all diagnosed cases children are "less capable" of spreading the virus, and are at "very low risk" of getting ill from the disease. WHO 22 European Union countries where schools were partially reopened, there hadn't been a significant increase in cases, including among staff. These countries all opened up schools to different extents
SARS-CoV-2 . low levels of antiviral cytokines ,type-I interferons(IFNs) suppress Th1 and favour Th2 responses. Dys-regulation T cell subtypes. the adaptive immune system Decrease B lymphocytes and their antibodies production. Increase pro-inflammatory cytokines and chemokines , with T cell depletion. pulmonary inflammation and extensive lung damage. SARS-CoV2 entry,replication,and release: binds ACE2 cell receptor using spike glycoprotein(S protein) enters the cell cytoplasm RNA genome replicate,and forms and releases new viral particles. Pathogenesis
PATHOGENESIS CONā¦ā¦.. Antigen presentation :The viral antigen APCs that present MHC. stimulates both cellular and humoral immunity. Immune effector cells cytokines and chemokines (a cytokine storm) acute respiratory distress syndrome(ARDS), single or multiple organ failure, and eventually death.
PATHOGENESIS Contā¦.. Cytokine storm driven by a dysregulated immune response hyper cytokinemia multi organ failure. In severe infection: lymphocyte counts( CD4andCD8Tcells ), IL-6 and IL-10,D-dimer and FDP levels, thrombosis and multi-organ injury. Abnormal coagulation: due to high expression of ACE2 receptors in vascular endothelial cells. MicroCLOTS :(microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome) associated with the inflammatory reaction and the microvascular pulmonary thrombosis.
Protective immunological mechanism in children Firstly :ACE2 expression lower in pediatric population. ACE2 gene is located on the X-chromosome. Circulating ACE2 levels are higher in men than in women Secondly :With ageing, due to antigen stimulation and thymic involution T cell subset shifted from naĆÆve T cells to central memory T cells, effector T cells and effector memory T cells .
This process is accompanied by the loss of expression of co-stimulatory molecules such as CD27 and CD28, with increased susceptibility to infections Thirdly , simultaneous presence of other viruses in the mucosa lungs and airways, common in young children, can let SARS-CoV-2 virus compete with them and limit its growth.
Pathology severe COVID-19 lung damage was manifested Diffuse Alveolar Disease (DAD) with severe capillary congestion. vascular dysfunction, in lung and other tissues. capillary congestion, necrosis of pneumocytes , hyaline membrane, interstitial edema , pneumocyte hyperplasia, and reactive atypia . Platelet-fibrin thrombi in small arterial vessels were the expression of intravascular coagulopathy . Lung infiltrates expressed as macrophages in alveolar lumens and lymphocytes in the interstitium
CO- MORBID CONDITIONS Congenital heart disease Cerebrovascular diseases RSV infection Recurrent wheezing Bronchial pulmonary hypoplasia Bronchial asthma Severe malnutrition Immunodeficiency or immunocompromised status CKD undergoing dialysis Chronic liver disease Diabetes mellitus Severe obesity Cystic fibrosis,Hemoglobinopathies,JIA,SLE,Kawasaki
Critical Cases Children with a history of contact with severe SARS-CoV-2 infected cases,or with underlying conditions. congenital heart disease, bronchial pulmonary hypoplasia ,respiratory tract anomaly, abnormal hemoglobin level, severe malnutrition immune deficiency or immunocompromised status (under long term use of immunosuppressants) who meet any one of the following criteria: 1. Dyspnea: respiratory rate ā„60times/min for less than 2 months old ; ā„50times/min for2ā12months old; ā„40times/min for1ā5years old; ā„30times/min for>5years old(after ruling out the effects of fever and crying).
2. Poor mental response, lethargy, disturbance of consciousness,and other changes of consciousness. 3. Abnormally increased enzymatic indexes, such as myocardial enzymes, liver enzymes, lactate dehydrogenase. 4. Unexplainable metabolicacidosis . 5. Chest imaging findings indicating bilateral or multi-lobe infiltration, pleural effusion, or rapid progression of conditions during a very short period.
CLINICAL SYMPTOMS Fever (41.5%) Cough (48.5%) sore throat (46.2%) Diarrhea (8.8%) Conjunctivitis Loss of taste and/ or smell Headache Dyspnea in severe case Myalgia Fatigue (7.6%) Rhinorrhea (7.6%) Vomiting (6.4%) Nasal congestion (5.3%) Abdominal pain Rash
Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19 Preliminary case definition Children and adolescents 0ā19 years of age with feverĀ >Ā 3 days AND Ā two Ā of the following:Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Rash or bilateral non-purulent conjunctivitis or muco-cutaneous inflammation signs (oral, hands or feet). Hypotension or shock. Features of myocardial dysfunction, pericarditis, valvulitis , or coronary abnormalities (including ECHO findings or elevated Troponin/NT-proBNP), Evidence of coagulopathy (by PT, PTT, elevated d-Dimers). Acute gastrointestinal problems (diarrhoea, vomiting, or abdominal pain ).
AND Elevated markers of inflammation such as ESR, C-reactive protein, or procalcitonin .Ā AND No other obvious microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock syndromes. AND Evidence of COVID-19 Ā ( RT-PCR, antigen test or serology positive), or likely contact with patients with COVID-19.
Investigations
Reverse transcription polymerase chain reaction (RT-PCR) Genetic sequencing of respiratory tract or blood samples is highly homologous with the known SARS-CoV-2, but this is not done routinely. Although antibody dependent tests are not recommended yet by the Govt. of Bangladesh, but many countries are using these test as initial screening To cofirm Diagnosis
Sputum and other lower respiratory tract specimens have a high positive rate of nucleic acids and should be collected preferentially. SARS-CoV-2 preferentially proliferates in type II alveolar cells (AT2) and peak of viral shedding appears 3 to 5 days after the onset of disease. Therefore, if the nucleic acid test is negative at the beginning , samples should continue to be collected and tested on subsequent days.
Sensitivity of RT PCR- 71-98% The sensitivity may vary due to- Specimen site Quality of specimen Temperature of storage Collection techniques Transport Method BMJ journal
To Asses clinical conditions Complete blood count (CBC) Leucopenia (9-25%) and lymphopenia (83%), Severe patients have a progressively decreased number of peripheral blood lymphocytes. A ratio of Neutrophil to lymphocyte more than 3.5 is a prognostically poor sign. Leucocytosis (24-30%), thrombocytopenia Markers of infection Raised ESR, CRP, Ferritin , IL-6. Procalcitonin low/normal; may be high (> 0.5 ng / mL ) if there is secondary bacterial infection Coagulation profile D- dimer , PT, aPTT and fibrinogen levels (if possible). Raised D- dimer indicates severe disease and worse outcome
RFT Raised Urea/ creatinine in severely sick children LFT Raised SGPT/SGOT (12-14% cases) indicates severe disease Cardiac markers Raised troponin -I (12% cases) Other organ markers LDH, CPK and myoglobin raised in some patients To exclude other disease Dengue IgG and IgM and other related investigations
Normal or low TC of WBC, Lymphopenia , High CRP, Low Procalcitonin ; if these are associated with bilateral pneumonia in Chest x-ray or GGO in CT scan of Chest: Diagnosis is COVID-19 during this epidemic.
Chest X-ray (CXR) In the early stage: may be normal or multiple small patches or plaques and interstitial changes (haziness), mostly obvious in the lung periphery. With deterioration: bilateral multiple ground-glass opacity and/or infiltrating shadows. In severe cases: Lung consolidation. ļ§ Pleural effusion is rarely seen.
Chest X ray showing bilateral multiple ground-glass opacity of a Covid patient
ARDS in Covid
Indication of Chest CT scan 1. Bilateral lung involvement on CXR. 2. ICU admission. 3. In a patient who has not responded to primary treatment and is developing respiratory distress. 4. The CXR is getting worse. 5. Symptomatic patient in contact with definitive patient with COVID-19.
HRCT Scan is highly preferable. Following are the classical CT findings Bilateral involvement in most patients Multiple areas of consolidation Ground-glass opacities (GGO): bilateral, subpleural , peripheral Crazy paving appearance (GGOs and inter- /intra-lobular septal thickening) Bronchovascular thickening in the lesion Traction bronchiectasis
USG of chest- there are specific sonographic findings however it requires a skilled operator who has training on Pulmonary Ultrasonography . All CXR, CT, sonography are nonspecific. Patchy ground-glass opacities may be caused by a broad range of disease processes (e.g. viral and bacterial pneumonias). Ultimately, the imaging is only one bit of information which must be integrated into clinical and epidemiological context.
Infants who cannot be tested, should be treated as if they are positive for the virus for the 14-day observation period. The mother should continue to maintain precautions until she meets the criteria for noninfectivity .
Management
Treatment venue will be determined according to severity of the disease: ⢠Suspected and confirmed cases should be isolated and preferably treated at designated hospitals with effective isolation. ⢠A mild case may be treated in isolation in a single room at home . ⢠Mild cases with comorbidity /risk factors , Moderate & Severe cases should be treated in COVID-19 hospital ⢠Critical cases should be admitted to ICU as soon as possible
General management Bed rest and strengthening support therapy. Ensuring sufficient calorie intake Monitoring water and electrolyte balance to maintain internal environment stability Monitoring vital signs and oxygen saturation. Timely providing effective oxygen therapy
Routine assessment Changes in childrenās conditions. Regularly monitor vital signs, SpO2, etc. Identify the severe and critical cases as early as possible.
Symptomatic proven case Admit In Treatment Discharge Mild Designated COVID isolation room Symptomatic treatment Discharge if 72 h afebrile or 7d after symptom onset and two samples negative 24 h apart followed by home quarantine for total 14 d Moderate Designated COVID isolation room Supportive care, oxygen, Oseltamivir Clinical improvement and two negative SARS-CoV-2 PCR tests 24 h apart Treatment Based on Severity of Disease in COVID-19
Symptomatic proven case Admit In Treatment Discharge Severe COVID ICU Provide nasal prong oxygen, escalate to invasive ventilation if worsening. ļ§ Avoid HFNC/NIV ļ§ Anti-viral drugs as per protocol ļ§ Supportive care Clinical improvement and two negative SARS-CoV-2 PCR tests 24 h apart Treatment Based on Severity of Disease in COVID-19
Symptomatic proven case Admit In Treatment Discharge Critical COVID ICU In addition to above ļ§ Intubate based on clinical/ blood gas / radiological features ļ§ Use all airborne precautions ļ§ Ventilation with ARDS protocol ļ§ Other organ support ļ§ Once improving, wean from ventilation and extubate as per protocol Clinical improvement and two negative SARS-CoV-2 PCR tests 24 h apart HFNC HFNC: High-flow nasal cannula , NIV: Non-invasive ventilation, ICU: intensive care unit, ARDS: Acute respiratory distress syndrome.
Criteria for ICU care Severe or critical disease Respiratory failure requiring mechanical ventilation Shock Combined with other organs failure
Treatment of severe and critically ill cases: Indication of early elective intubation : Increased airway secretions Worsening hypercapnia , acidemia , respiratory fatigue or those with altered mental status PaO2/FiO2 ratio <300, SpO2/FiO2 ratio <220 Failed trial of non-invasive mechanical ventilation (NIV) for 2 hours Cannot tolerate NIV
Mechanical ventilation strategy for ARDS High PEEP 10-15, low TV 4-6 ml/kg ideal body weight (not patients present weight), high RR, short I:E ratio Prone nursing 12-18 hrs/day, especially if PaO2/FiO2 ratio <150. Minimum ET tube and ventilator disconnection. Monitor progression of the disease with PaO2/FiO2 ratio, SpO2/FiO2 ratio and oxygenation index (OI). Adequate sedation, analgesia Muscle relaxant is indicated if PaO2/FiO2 ratio <150. High frequency oscillatory ventilation (HFOV) and Extra-corporeal membrane oxygenation (ECMO): Not included in this guideline due to lack of availability in Bangladesh.
Prone Nursing in Covid patients
Oxygen therapy Start preferably with low flow oxygen by nasal cannula (1-4 L/min) when SpO2 <92% or respiratory distress to keep SpO2 94-97%. A triple layer mask should be used to cover the mouth and nose of the patient over the nasal cannula , especially during transport, unless the child does not tolerate. Alternately oxygen by mask (preferably Venturi mask if available) can be used. Oxygen hood can be a good option for neonate and early infant.
Oxygen delivery devices
Nasal Cannula Most commonly used Maximum flow rate 6 L/min Additional comfort while speaking and feeding Prolonged use of nasal cannula may lead to drying of mucosa and crusting of secretions and may lead to epistaxis
Simple face mask Minimum flow rate 5 L/min and maximum 10 L/min Needs to be removed while eating and speaking Difficult to get a proper seal Possibility of dryness of eyes and accidental injury to eyes
Partial rebreathing masks no valve present at mask and in between reservoir & mask Minimal flow rate 8 L/min Some amount of rebreathing is allowed Especially helpful in situations where oxygen supply is less Malfunction of the equipment may lead to CO2 build up and suffocation.
Non- rebreathing masks Valve present between reservoir and mask Minimal flow rate 12 L/min Prolonged use is not recommended and is also uncomfortable
Venturi masks
Venturi masks Advantage of delivering exact FiO2
Oxygen hood Useful to provide FiO2 >40% in neonate and young infant Difficult to provide in older children The oxygen delivered needs to be humidified and warmed.
High flow nasal cannula (HFNC) Delivers a flow rate up to 8 L/min in infants, 25 L/min in younger children and 60 L/min in older children and adults It can deliver FiO2 0.21 ā 1.0
High frequency oscillatory ventilation
Extra-corporeal membrane oxygenation
Fluid resuscitation
Choice of fluid resuscitation Balanced/buffered crystalloids e.g. Plasmalyte (not available in Bangladesh), Ringers lactate or Hartmann solution are first choice, then 0.9% saline. Synthetic colloids, albumin, FFP should not be used. Vasoactive drugs: Start Adrenaline infusion (0.05-0.2 mcg/kg/min) if there is no or inadequate response after fluid resuscitation for shock or hypotension. Maintenance fluid: Conservative fluid management with 70-80% of the daily requirement and avoidance of fluid overload 0.45% saline or Ringers lactate or Hartmann saline can be used as maintenance fluid
Treatment of organ dysfunction Myocarditis : Management includes inodilators like milrinone , diuretics, immunomodulators ( methylprednisolone and IVIG). Acute kidney injury (AKI): May developed in 7% and renal replacement therapy may be necessary
Other Supportive care Adequate nutrition, Early enteral nutrition within 24 hours and achieve full feeds by 48 hours Appropriate sedation-analgesia Transfusion trigger hemoglobin <7 g/ dL if stable hemodynamics and oxygenation Target hemoglobin 10 g/ dL in refractory hypoxemia or unstable shock
Venous thromboembolism (VTE): Till now no evidence is available for Paediatric patients. As per adult studies, unless contraindicated (e.g. active bleeding or platelet count <30,000/ cmm ), prophylaxis to prevent VTE by heparin infusion (10-20 unit/kg/hr, can be increased upto 50 unit/kg/hr) to keep APTT at least twice than normal.
Specific therapy No drug should be used without recommendation or without fulfilling appropriate research enrollment. Few evidences are just emerging from a number of clinical trials from adult patients regarding beneficial effects of Remdesivir , Lopinavir / Ritonavir , Favipiravir , Chloroquine , Azithromycin and a number of other agents. Lopinavir / Ritonavir along with Chloroquine should be avoided in combination. Hydroxychloroquine and Azithromycin combination also should be avoided due to possibility of fatal arrhythmia
Antibiotics Broad spectrum antibiotic to be used in specific cases only. But avoid irrational use of antibiotics. 1st line antibiotic: Ampicillin 50mg/kg IV/IM 6 hourly plus Gentamicin 7.5 mg/kg IV/IM once daily for 5-7 days. 2nd line antibiotic: Ceftriaxone 50-80 mg/kg IV once daily for 5-7 days. Additional antibiotic : In severe cases or strong possibility of infection with gram positive organism, Vancomycin 45-60 mg/kg/day in 3 divided doses can be added along with Ceftriaxone . If atypical organism is suspected then Clarithromycin (15 mg/kg/day in 2 divided doses IV or PO) can be added.
ADJUVANT THERAPY Corticosteroids: Should not be used routinely. Short period (3ā5 days) of methylprednisolone , maximum 1ā2 mg/kg/day can be considered in severe systemic inflammatory response, significant dyspnea with wheeze with or without ARDS, septic shock etc. Intravenous immunoglobulin: Can be used in severe cases when indicated, but its efficacy needs further evaluation. Convalescent plasma: Study has been adopted in Bangladesh, though detail guideline not yet available.
DISCHARGE CRITERIA The body temperature returns to normal longer than 3 days without antipyretics. The respiratory symptoms improve obviously. The detection Covid-19 RT-PCR test is negative for two consecutive times (the sampling interval is at least 1 day) In any case all discharged patients to be home isolated for 14 days.
POST DISCHARGE Medication after Discharge Treatments for symptoms can be applied if patients have mild cough, poor appetite, thick tongue coating, etc. Those who are on antiviral drugs, can be used after discharge for patients with multiple lung lesions for 3 days after their RT-PCR tested negative.
Home isolation Patients must continue two weeks of isolation after discharge. Recommended home isolation conditions are: Independent living area with frequent ventilation and disinfection Patients and their family members must wear masks and wash hands frequently Body temperature are taken twice a day (in the morning and evening) and pay close Attention to any changes in the patientās condition.
PROGNOSIS Children <1 year of age may experience greater disease severity. Children mostly have good prognosis, and in mild cases recover 1ā2 weeks after disease onset. Raised D- dimer , ferritin , troponin , cardiac myoglobin and lymphopenia is associated with bad prognosis.
Fate of Covid 19 As we are still in the pandemic, and at a relatively early stage of a new disease, it is too early to tell what COVID-19 survivors are likely to experience in a yearās time. A study in Hong Kong one in two SARS survivors had much poorer exercise capacity and health status than those who had never had the disease. Only 78% of SARS patients were able to return to fullātime work 1 year after infection . AnotherĀ study in Hong Kong, revealed that 40% of people recovering from SARS still had chronic fatigue symptoms 3.5 years after being diagnosed. Viral infections such as SARS and Epstein-Barr virus are known to trigger chronic fatigue syndrome that can last for months or years.
Antiviral drug, hydroxychloroquine , azythromycin , adjuvant therapies have not been proven to be beneficial in COVID-19 newborn
If the neonate is suspected as COVID-19 positive Admit infant to an area separated from unaffected infants Thoroughly investigate neonates with symptoms of COVID-19 infection for other common diseases that may have similar clinical presentations Testing should be done first at 24 hours of age follow-up testing of nasopharynx specimens should be done at 48-72 hour intervals until two consecutive tests are negative.
Drug therapy according to Severity
Taking care of minds is also very important!
Infection prevention and control
Avoid to touch T zone of face
Ensure wearing Mask! The C.D.C. has said that cloth face coverings should not be placed on children under 2 , nor should they be used on anyone who has trouble breathingĀ
Cough ettiquette
Protection from Aerosol All aerosol generating procedures/events require donning of personal protective equipment and if possible a negative pressure room. Where possible, a nebulizer may be replaced with an MDI and spacer for administration of bronchodilators. NIV generates droplets >10 μm in size and most fall on local surfaces within 1-meter distance. HCWs who are providing NIV, chest physiotherapy or working within 1 meter of an infected patient should have a high level of respiratory protection. In infants, while HFNC is being given they can be placed in an oxygen hood to minimize dispersion of aerosol.
Vaccination Update
In the world thousands of scientists are working on more than 150 vaccines for Covid19. but till now no vaccine achieved expected goal. Scientists expecting success within 2021.
EPI Vaccination must Go On!
Breast feeding by Covid+ve mother COVID-19 positive mother should express breast milk after wearing mask and appropriate washing of breast and hand. Caregivers who are not infected will feed the breast milk with cup and spoon .
Reinfection
Reinfection with SARS-CoV-2 seems unlikely taking into consideration our knowledge on viral neutralizing antibody duration from past respiratory illnesses, the type of specimen collection and technical errors associated with each component of swab testing, the methods used before discharging these patients, the presence of fecal viral RNA without evidence of replication-competent virus in fecal swabs. we must maintain vigilance during the convalescence period also and must take into consideration the probability of genetic mutations as observed rather than re infection by the same strain.