New Covid 19

Guidelines
Orientation
LDH
VIRAL STRUCTURE
SARS-COV-2 Virion
• Coronaviruses are
enveloped viruses,
minute in size (65–
125 nm in diameter) and
contain a single-stranded
RNA as a nucleic
material, size ranging
from 26 to 32kbs in
length
 SARS-CoV-2 is an RNA virus with a Crown-like structure
composed of an outer layer of ‘spike’ Proteins
• Spike Protein
• Outer protein of SARS-CoV-2
• Target of all vaccines and monoclonal Abs
• Mutations give rise to different variants
• Nucleocapsid Protein
• Most abundant protein of SARS-CoV-2
• Target of rapid antigen diagnostic tests
• RNA
• Genetic material inside virus
• Target of all PCR-based diagnostic tests
• Codes for all virus proteins, so useful for genetic
sequencing to identify different variants
TRANSMISSION
 SARS-CoV-2 transmission is a function of intensity
and duration of exposure
SARS-CoV-2 transmission is via Aerosols and Droplets
How? Most transmission is from symptomatic
persons via droplets, aerosols, and through
contact

When? Pre-symptomatic transmission can

occur from people who are infected and
shedding virus but have not yet developed
symptoms. Asymptomatic transmission can
also occur. This refers to transmission
through people who are infected and
shedding virus but have not and do not ever
develop symptoms.

Where? Primarily among close contacts;

• Droplets > 100 microns (μm) fall to ground usually within 1 m of travel Transmission can be amplified in closed,
• Aerosols < 100 microns (μm) may float in air for hours and be inhaled
crowded, indoor settings

1) https://www.science.org/doi/10.1126/science.abd9149 2) WHO: Transmission of SARS-CoV-2: implications for infection prevention precautions

 SARS-CoV-2 is mainly spread through aerosol and droplet
transmission; Masks, ventilation and air filtration can prevent
infection
Universal masking ensures minimum exposure Universal masking reduces population transmission

• SARS-CoV-2 can be bound up in particles of all sizes, ventilation, air particle filtration, and the use of high-efficiency masks
(N95, KN90, KN95) are effective COVID-19 prevention measures. Don’t forget: good indoor air quality is important!

https://www.pnas.org/doi/10.1073/pnas.2009637117
Given the routes of transmission, numerous interventions exist
to mitigate COVID-19 associated morbidity and mortality

Prevent Infection Prevent Severe Disease

Social distancing
Lockdowns
Improved indoor air quality
High-quality masks
Symptomatic testing
Isolation of positive cases
Population-based screening
Risk factor modification
COVID-19 Vaccines and boosters
Early diagnosis and treatment
Anti-viral medications (early)
Anti-inflammatory medications (late)
Supportive care
CLINICAL FEATURES
 The viral and inflammatory response phases are defined by
different clinical characteristics
Asymptomatic or Pre-
symptomatic Mild Illness Moderate Illness Severe Illness Critical Illness
Features Positive SARS-CoV-2 Mild symptoms (e.g Clinical evidence of Oxygen saturation < Respiratory failure,
test; no symptoms fever, cough, sore lower respiratory tract 93% ; respiratory rate shock, and multiorgan
throat) diseases; oxygen >30 breaths/min; lung dysfunction or failure
saturation >93% infiltrates >50%
Isolation Yes Yes Yes Yes Yes

• Anti-viral agents must be used during time of viral replication (mild to moderate illness) and are ineffective once
disease has progressed into inflammatory phase

Gandhi RT, et al. N Engl J Med. 2020;383:1757-1766

Symptoms of acute COVID-19 vary between people and
variants, but the most common symptoms are as follows
Less Frequent Symptoms

Nausea

Diarrhea

Anosmia (loss of smell)

Ageusia (loss of taste)

Anorexia
Clinical Features
• Incubation period:
Mean: 4 days (IQR 2-7 days)
Range: 2 - 14 days following exposure
• One-week prodrome
• Symptoms:
• Fever (77–98%)
• Cough (46%–82%)
• Myalgia or fatigue (11–52%)
• Shortness of breath (3-31%)
• Olfactory & taste disorders (34%)
Very non-specific

Huang et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020 Jan 24.
Wang et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan. Published online February 7, 2020.
Chen et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Jan 30
Holshue et al. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020 Jan 31.
Huang et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Jan 24.
 COVID-19 Disease Severity Classification is useful to determine
appropriate level of care treatment regimen
1 2 3 4

Mild Moderate Severe Critical

Signs and symptoms: fever, Evidence of lower respiratory Respiratory rate >30 breaths
cough, sore throat, malaise, disease by clinical assessment Respiratory failure
per minute
headache (non exhaustive) or imaging

Oxygen saturation < 93% on

NO dyspnea Oxygen saturation >93% on room air at sea level (or Sepsis /
NO shortness of breath room air at sea level decrease from baseline by Septic shock
>3%)

PaO2/FiO2 <300 mmHg

Normal CXR Lung infiltrates <50% Multi-organ dysfunction
Lung infiltrates >50%

Requires Inpatient Management

Appropriate for Outpatient Management

Untreated patients may progress through various severity classifications over time

CDC. Accessed October 25, 2022. https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/.

There are many factors which influence symptoms, disease
progression, and outcomes
Age
• Significant increase in death > age 50
• Less severe, but not completely benign in
children
Vaccination Status
• Consistently higher hospitalization/ death
in unvaccinated people
• Data show that booster vaccines continue
to reduce severe disease
Early Treatment
• Early anti-viral therapy can reduce severe
disease by 80-90%
Presence of Comorbidities
• Combination effect of multiple co-
morbidities,
• Metabolic disease: diabetes mellitus,
obesity, Cardiopulmonary disease:
hypertension, coronary artery disease,
asthma/COPD,
• Immunosuppression: HIV disease,
iatrogenic (chemotherapy,
corticosteroids),
• Pregnancy: adverse birth outcomes and
more, severe disease
At risk for clinical deterioration
• Old age/elderly persons - >50years of age
• Comorbidities (COVID-19 specific):
• Diabetes, hypertension, cardiovascular disease
• Comorbidities (from other resp illnesses):
• Chronic lung disease
• HIV CD4 <200
• Solid organ or bone marrow transplant
• Neurological disease
• Advanced liver disease
• End stage renal disease
• Other immunosuppressive therapies
INVESTIGATIONS
1

There are two main types of viral tests to diagnose a current

COVID-19 infection: rt-PCR and antigen tests
Antigen RDTs • detect the SARS-CoV-2 virus antigen(s) in patient samples from upper respiratory
tract (e.g. nasopharyngeal)

• easy-to-use, rapid tests that can be used at or near the point of care, without
the need for laboratory infrastructure or expensive equipment

• Turnaround time = 15-20 minutes

• Highly specific, but slightly less sensitive than PCR

rt-PCR (NAAT) • detect the presence of viral RNA in patient samples from the respiratory tract
but also in oral fluid, saliva and stool

• typically require well-resourced laboratory facilities, multiple reagents, sample

referral systems and skilled personnel

• Turnaround time varies on laboratory flow, but typically 1-3 days

• Highly specific and extremely sensitive (may stay positive for weeks after COVID-
19 illness)
Timely Testing for SARS-CoV-2
• Timely testing ensures the effective • ANY positive test should be
use of use antivirals (EARLY within 5-7 interpreted as definitive and positive
days of symptom onset) • Long-standing positive test results
• Use rapid antigen test for >10 days following infection may
symptomatic individuals and close represent noninfectious viral
contacts of individuals who are particles
positive for COVID-19 • In an event of negative COVID-19 test,
• Rapid antigen tests have higher rate repeat rapid antigen test in 3-5 days
of false-negative results compared
with PCR tests
• PCR tests are definitive diagnostic test

cdc.gov/coronavirus/2019-ncov/hcp/testing-overview.html. Last updated September 28, 2022.

Some causes of false negative results
o Swabbing too quickly
- insufficient amounts of viral genetic or antigenic material for detection
o Prolonged time from specimen collection to testing
- uncontrolled temperature during this time

oCotton, calcium alginate swabs, or swabs with wooden sticks

- may inactivate viruses and inhibit the PCR
Testing at the Facility and Community
• Testing for COVID-19 at a Health Facility
• All admitted patients with medical, paediatric, or oncological conditions are
tested for COVID-19 as recommended

• High index of suspicion at all times

• Bi-directional screening of TB in patients suspected of COVID-19

• Testing for COVID-19 within the Community
• Rapid tests for COVID-19

• “test and treat” strategy

 Takeaway:
• Both PCR and Antigen tests can detect SARS-CoV-2 right before symptom onset.
• PCR, due to increased sensitivity will stay positive for weeks after infection, while Antigen only stays
positive during periods of very high viral burden.
• IgM and IgG tests in blood do not turn positive until 1-2 weeks after symptoms and therefore are
not useful in a test and treat setting.
 Plain chest Radiographic findings in COVID-19

• Ambiguous
• Normal
• Groundglass opacifications
• Bilateral multifocal consolidation can be seen in severe
patients,
• Peripheral, lower lobes
• pleural effusions are very rare
• May present with “white lung” in severe cases
Radiological Findings From Zambian
Patients
Differential diagnoses
Influenza
Conditio Sputum
Investiga
(flu)n mcs
tions
TB Sputum
Atypical Gene
pneumoni
Xpert
a
Urine
PCP
Fungal LAM
/bacterial Blood
pneumoni culture
a CXR
Heart FBC
failure HIV/
Myocardia CD4/VL
l infarction ECG,ECH
Pulmonar O
y
+/- CT
embolism
chest
Tuberculosis & COVID-19
• Tuberculosis and COVID-19 share many characteristics
Risk groups:
• older persons, diabetics, COPD, chronic kidney disease, etc.

Clinical features:
• cough, fever, pneumonia in some cases SOB

Modes of transmission:
• in close/crowded settings, via respiratory secretions – either
airborne or droplet
Tuberculosis & COVID-19 cont’d
• TB should be part of the differential diagnosis in someone with suspected
or confirmed COVID-19 in Zambia

 This is particularly true of persons with post-COVID-19 where persistent cough or

other symptoms could signify co-infection with Tuberculosis
 Always remember TB particularly in People living with HIV

• Additionally, patients attending TB clinic should be considered for

COVID-19 testing
 Newly diagnosed patients
 patients on treatment with new or worsening respiratory symptoms
Management
5
Branded Paxlovid is a co-pack of 300 mg (2 150 mg tablets) nirmatrelvir
and 150mg ritonavir which are to be taken twice daily for five days

Administration Instructions
INITIATED WITHIN
Administration should be as early as possible in the time course of the disease and administered within 5 days of symptom onset
5 DAYS
of SYMPTOM ONSET Patients should take 2 tablets of nirmatrelvir with 1 tablet of ritonavir by mouth 2 times each day (in the morning and in the evening) for 5 days.

3 For each dose, all 3 tablets should be taken at the at the same time, and tablets should be swallowed whole (not chewed, broken, or crushed).
PILLS Paxlovid (nirmatrelvir/ritonavir) can be taken with or without food.

2X Patients should be instructed to not stop taking the treatment without first talking to their healthcare provider, even if they are feeling better.
/ DAY
Providers should discuss drug-drug interactions and ensure normal renal function in patient.
FOR

5 DAYS

28
Paxlovid Clinical Guidance
1. Mild to moderate Covid-19
• e.g., No oxygen requirement
• ≈ Outpatient use
2. ≥1 risk factor for progression to
severe disease
• Do not use if:
• No risk factors
• Symptoms onset >5 days ago
• Asymptomatic infection
Baricitinib
• Baricitinib is a selective Janus kinase 1 and 2 inhibitor
• has both anti-inflammatory and potential antiviral activity
• Recommendations: Among hospitalized adults with severe COVID-19 having
elevated inflammatory markers but not on invasive mechanical ventilation
and severe COVID-19 patients who cannot receive a corticosteroid (which is
standard of care) because of a contraindication, the IDSA guideline panel
suggests use of Baricitinib with Remdesivir
• Dose
• Baricitinib 4 mg daily dose for 14 days or until discharge from hospital
• Baricitinib appears to demonstrate the most benefit in those with severe COVID-19
on high-flow oxygen/non-invasive ventilation at baseline
Tocilizumab
• Is a recombinant humanized anti-interleukin 6 (IL-6) monoclonal
antibody.
• Tocilizumab binds to both soluble and membrane-bound IL-6
receptors, and has been shown to inhibit IL-6-mediated signaling
through those receptors.
• Recommended in addition to standard of care, including
corticosteroids, for progressive severe or critical disease in patients
with COVID-19 pneumonia.
• Tocilizumab should be given only in combination with
dexamethasone (or another corticosteroid at an equivalent dose)
Tocilizumab
COVID-19, hospitalized adults and pediatric patients (≥2 years of age):
• Weight <30 kg: 12 mg/kg as a single IV infusion over 60 minutes
• Weight ≥30 kg: 8 mg/kg as a single IV infusion over 60 minutes
• Maximum dosage: 800 mg per infusion
• If clinical signs or symptoms worsen or do not improve after the initial dose,
consider administering an additional dose at least 8 hours after the initial dose
Systemic Corticosteroids
Antibiotic use among hospitalized
COVID-19 patients
• No role for the use of antibiotics for management of COVID-19 in the
absence of bacterial co-infection
• Unnecessary antibiotic use exposes patients to adverse outcomes and
may contribute to antimicrobial resistance

• Objective: to report on use of antibiotics among hospitalized COVID-

19 patients in Zambia
Key Takeaways
• Effective treatment that reduces hospitalization by 85% is available for
outpatients at higher risk with mild to moderate acute COVID-19
• Timely diagnosis with prompt testing is essential to early treatment in <5 to 7 days
• Risk assessment is key to identify patients eligible for treatment
• Age >50 years is the strongest predictor of severe disease
• Treatment Options
• Paxlovid for Ambulatory/outpatients
• Updates on the use of Remdesivir for children and in outpatient settings
• Role for Steroids as first line for hospitalized patients and baricitinib as salvage therapy
• Clarification on therapeutics that do not work such as Azithromycin