Now that the second wave of COVID is here, here are new updates to the guideline on assessing COVID-19 patients in need of emergency care. The guidance also focuses on investigations to perform in hospitalised patients, lab parameters that can help with planning dosage, and clinical pearls that can act as game-changers.

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How to assess need for emergency care action

Here are the situations that may warrant emergency care:

• Laboured respiration associated with an anticipated difficult airway
• Respiratory rate >30, inability to speak full sentences, cyanosis, or SpO2<85 per cent on room air; ABG P/F ratio< 250
• Even after fluid resuscitation, systolic blood pressure is less than 90 mmHg; agitated, disturbed (or comatose) with respiratory distress; initial MODS: two or more organ failures
• CURB-65 score of 3 or more (confusion, urea >40, RR>24, BP>90, and Age >65); in COVID-19 patients, CURB65 may be a helpful prognostic factor that could be used to rapidly triage acute patients in clinical care practice
• Q SOFA scoring – at least two of HAT (hypotension, altered mentation, tachypnoea)

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Monitoring of cases

• Vital parameters are RR, BP, HR, assess dyspnoea, SpO2
• Lab parameters CBC, RFT, LFT, NLR. Troponin, CPK MB, ECG as and when indicated
• ABG and CXR – daily in moderate to severe disease

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Warning signs

Development of these warning signs indicate likely deterioration:

• The ratio of neutrophils to lymphocytes is greater than 3.5
• Increased CRP/Ferritin/D-Dimer/LDH levels
• A PF ratio of less than 300
• Eosinopenia (Zero eosinophilic syndrome)

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When is it necessary to maintain vigilance?

• Fever greater than 101°F with medications or greater than 103°F without antipyretics
• Coughing that persists until day 3
• Breathlessness that appears suddenly (or exertional SOB)
• CRP levels rapidly escalate (>10 mg/L)
• On CT, there was more than 50% lung participation (13/25 score)
• Sensorium alterations

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Investigations to evaluate in hospitalised patients

• CBC with PS
• Analyze RDW (red cell distribution width) and NLR (neutrophil-lymphocyte ratio), as well as CRP and LDH
• LFT, KFT, RBS, HbA1c, and urine R/M. HbA1C has been demonstrated in a few research to be a clear indicator of COVID19 intensity
• Blood culture (two sets), serum procalcitonin
• ABG
• Sputum gram stain and C/S (After RT PCR report)
• Nasopharyngeal swab for SARS-COV2 qualitative
• PCR CXR PA view/ screening, CT thorax if a diagnostic dilemma exists
• ECG
• D-dimer, Ferritin ➤ CPK-MB, NT Pro BNP, Trop I
• Before starting anticoagulation, review your PT, aPTT, and INR
• Echocardiogram in all elderly and in some particular patients

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Lab parameters in mild, moderate, and severe COVID

Lab parameters	Mild COVID	Moderate COVID	Severe COVID
Liver function tests	Normal	Slight abnormal	Moderately deranged
CRP	<20	20-50	>50
Neutrophil-Lymphocyte Ratio	<3.2	>3.2	>5.2
LDH	<300	300-400	>400
IL 6	<5	5-50	>50
Ferritin	<500	>500	>800
D-dimer	<0.5	0.5-1	>1

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What are the considerations for important lab tests?

Tests in the lab are guiding tools.

1. According to certain trials, CRP can be used as a steroid dosage guideline. Using a greater steroid dosage if the CRP is elevated. Remember that CRP may be caused by bacterial infection, urinary tract infection, or line sepsis in some cases. Steroids should not be increased in those situations. Reduce the dose of steroids gradually and supplement with the necessary antibiotic.
2. Procalcitonin, WBC, and culture results can be used as guidance.

The following factors contribute to the unreliability of IL 6 results:

• Laboratory procedures are not uniform. In various labs, the same sample will produce variable results
• Delays in transporting the obtained blood sample, as well as temperature sensitivity, affects IL 6 levels
• During a patient's follow-up, select the same lab/assay
• Several stable patients will have hundreds or thousands of IL 6 values that are incorrect

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What is the role of LDH?

Spike in LDH indicates that cells are dying. LDH is an enzyme that converts lactate to pyruvate in the cells of most tissue, and its levels rise after tissue breakdown. Hemolysis, chemotherapy, major infections and sepsis, liver disorders, hematologic cancers, and a variety of other health conditions all have elevated serum LDH levels.

There is already a lot of evidence that serum LDH levels can be used as a non-specific predictor of cellular death in a variety of diseases. A 62.5 U/L rise in LDH has reasonable sensitivity and high specificity for a significantly higher risk of disease progression. In COVID-19 pneumonia, LDH can be a useful follow-up attribute for detecting disease development and thereby assisting in risk stratification and early intervention.

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What is the role of Procalcitonin?

Procalcitonin is an inflammation mediator. The pro-peptide of calcitonin that has no hormonal function is known as procalcitonin. It is formed in the C-cells of the thyroid gland under normal conditions. PCT values in healthy individuals are insignificant (0.1 ng/mL). PCT levels can increase to more than 100 ng/mL during extreme infection (bacterial, parasitic, and fungal) with clinical symptoms, and is formed primarily by extra-thyroid tissue. PCT acts as an inflammation mediator.

In patients with uncomplicated SARS-CoV-2 infection, PCT values remain within reference ranges; any significant increase indicates bacterial co-infection, the emergence of a serious type of the disease, and a more complex clinical scenario. PCT in the early days is used to rule out secondary co-infections rather than to determine the seriousness of COVID-19 disease. Pre-existing comorbidities, such as CKD and heart failure, can influence PCT values, and baseline values may be greater.

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D DIMER- A notable indicator

After CRP and Procalcitonin, D DIMER is a significant predictor for treatment decisions. LMWH (e.g., Enoxaparin 40 mg daily) should be given to all admitted patients. All hospitalised patients should begin receiving a prophylaxis dosage of LMWH (enoxaparin or equivalent).

• For mild disease, the dose is 40 mg, and for severe illness, the dose is 1 mg/kg/day; DVT/PE can be suspected if the D-dimer level is greater than 1 mcg/ml
• For confirmed or highly suspected DVT or PE, start therapeutic anticoagulation (Enoxaparin 60 mg BD) before venous doppler/CTPA excludes the condition
• Every 2-3 days, check the D-dimer level; patients taking 60 BD, regular Hb, h/o Melena, and other similar medications should be monitored
• Consider prescribing an oral anticoagulant (e.g., Apixaban 2.5 mg BD or Rivaroxaban 10 mg OD for four weeks) for high-risk patients (modified IMPROVE-VTE score>4 or score>2 with d-dimer >2 times upper limit, old age, existing malignancy) at discharge

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Practical clinical/biochemical pearls that are potential game-changers

1. Identifying ‘day one of the illness' is critical in COVID-19.
2. Within the first nine days of symptoms, treat the infectious stage with an antiviral (such as Remdesivir).
3. To counteract immune overactivity, manage the immune system with anti-inflammatory steroids earlier in the pulmonary or inflammatory process. The pulmonary phase occurs following the viral replicable stage.
4. Lymphopenia is present in 80% of chronically ill adult COVID-19 patients, but in 25% of minor COVID-19 infection patients (observational), it implies that lymphopenia can be related to infection severity (changes in lymphocyte numbers in COVID-19 patients with critical infection imply a lower T cell count, a rise in naive helper T cells, and a decline in memory helper T cells).
5. Eosinopenia can be linked with adverse COVID-19 disease advancement.
6. NLR has been identified as a sepsis prognostic biomarker. NLR has been found to be a significant risk factor for severe illness. COVID-19 infection severity can be shown by NLR more than 3.5. NLR elevation may be caused by dysregulated inflammatory cytokine expression, an abnormal spike in pathological low-density neutrophils, and upregulation of genes involved in lymphocyte cell differentiation.
7. A red blood cell distribution width (RDW) of more than 14.5 is a basic prognostic indicator.

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Important points to consider

1. Clinicians should be cautious that certain patients can dramatically worsen 1 week after the onset of the disease.
2. The time it takes for COVID-19 to trigger acute respiratory distress syndrome (CARDS) is between 8 and 12 days.
3. Lymphopenia, neutropenia, elevated serum alanine aminotransferase and aspartate aminotransferase levels, elevated lactate dehydrogenase, high CRP, and high ferritin levels have all been linked to a higher degree of illness.

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