Journal of Postgraduate Medicine, Education and Research
Volume 56 | Issue 4 | Year 2022

Delayed Onset of COVID-19 Acute Respiratory Distress Syndrome (ARDS) in an Immunocompetent Patient

Uma N Saikia1, Suvradeep Mitra2, Neeraj Singla3, Nidhi Prabhakar4, Sanjay Jain5, Sunny Bhardwaj6, Pankaj Pant7

1,2Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

3,5Department of Internal Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

4Department of Radio Diagnosis & Imaging, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

6Department of Pathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

7Department of Telemedicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

Corresponding Author: Uma N Saikia, Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, Phone: +91 9876288554, e-mail: umasaikia@gmail.com

Received on: 28 May 2021; Accepted on: 26 June 2021; Published on: 31 December 2022

How to cite this article: Saikia UN, Mitra S, Singla N, et al. Delayed Onset of COVID-19 Acute Respiratory Distress Syndrome (ARDS) in an Immunocompetent Patient. J Postgrad Med Edu Res 2022;56(4):202-209.

Source of support: Nil

Conflict of interest: None

Keywords: ARDS, COVID-19, Immunocompetent, Late-onset.


The patient was a 58-year-old male who presented with a complaint of fever for 10 days of moderate intensity associated with dry cough and shortness of breath for 5 days which was insidious in onset. No associated history of chest pain, palpitations, decreased urine output, or altered sensorium was present. The patient had a history of diabetes mellitus (DM) type 2 recently detected. The family history was noncontributory. On examination, the patient was conscious and oriented, with blood pressure (BP) of 110/80 mm Hg and a pulse rate of 90/minute. The patient had tachypnea [respiratory rate (RR) 28/minute] with hypoxemia [oxygen saturation (SpO2) 80% on room air and 90% on non-rebreather mask 15 L/minute]. A respiratory system examination revealed B/L decreased air entry. The cardiovascular and central nervous system examinations were unremarkable.

Lab Investigations

The hemogram showed neutrophilia and thrombocytopenia [hemoglobin (Hb)—13 gm/dL, total leukocyte count (TLC)—11,000, differential leukocyte count (DLC) polymorphs—95%, and platelets—55,000/μL]. The renal function tests were within normal limits (WNL). The liver enzymes, that is, sepsis prediction and optimization of therapy (SGOT), serum glutamic pyruvic transaminase (SGPT) were mildly elevated at the day of admission (SGOT—53 U/L and SGPT—97 U/L), increased to 3–4 times and touching a peak of 7–8 times after 2 weeks of the intensive care unit (ICU) stay (SGOT—266 U/L and SGPT—356 IU/L) which was attributable to hepatitis, possibly viral and or drug-induced. The C-reactive protein (CRP) was elevated at the time of admission (38 mg/L), peaked at 151 mg/L in the 2nd week of illness, and reached a nadir of 10.7 mg/L (attributed to steroids and other immunosuppressive drugs received by the patient). It again peaked at 141.1 mg/L before the demise of the patient. The D-dimer and ferritin were raised throughout the hospital stay of the patient. The arterial blood gas (ABG) showed the partial pressure of oxygen (PO2)/fraction of inspired oxygen (FiO2) ratio of the patient on the day of admission as 97.4 and remained touching near normal during a hospital stay. However, just before the demise, the PO2 was <60. The partial pressure of carbon dioxide (PCO2) levels were normal at admission and the 2nd week of illness, and PCO2 levels were raised for a single day (92.5 mm Hg) attributed to mucous plug; however, preterminally PCO2 levels raised to 109 mm Hg which was attributed to the fibrotic phase of acute respiratory distress syndrome (ARDS).

The culture of sample essential thrombocythemia (ET) aspirate was sent on the 4th day of putting the patient on a mechanical ventilator as the patient developed fever and showed growth of Pseudomonas aeruginosa with the colony-forming unit (CFU) >10 × 5/mL. A 03/06—ET aspirate grew Acinetobacter baumannii with CFU >10 × 5/mL. On 21st June 2021, the ET aspirate showed growth of Acinetobacter baumannii with a new bug, Stenotrophomonas maltophilia. The bronchoalveolar lavage (BAL) fluid was sent for culture on 5th June and showed growth of Acinetobacter baumannii, and fungal culture grew Aspergillus. Meanwhile, the patient developed bed sores, and the swab culture grew Enterobacter aerogenes.

Other investigations done included:

  • Serum galactomannan—0.28 (normal).

  • 1–3 β-d-glucan—12, negative.

  • Cytomegalovirus (CMV) deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) —1.70 × 10 × 4 copies/mL.

  • Human immunodeficiency virus/hepatitis B surface antigen (HBsAg)/anti-hepatitis C virus (card test)—negative.

  • Lipid profile—cholesterol 187, triglycerides—195, high-density lipoprotein—57, low-density lipoprotein—97.2.

  • Hormonal profile—triiodothyronine—0.613 ng/mL, thyroxine—7.35 μg/dL, thyroid-stimulating hormone—0.206/μIU/mL.

  • Cortisol AM 28.1 nmol/L (171–536).

  • Hemoglobin A1c (HbA1c)—7.8% (29/05), 8% (26/06).

  • 25 (OH) D3—11.4 ng/mL

  • Prothrombin time/international normalized ratio—1.1 (88%) on 32/05 and 1.3 (82%) on 5/6.

  • Troponin T—8.10 pg/mL (29/05), 58 (25/06).

  • Creatine phosphokinase-MB—54 (24/06).

  • N-terminal pro-b-type natriuretic peptide—196.1 pg/mL.

  • Electrocardiogram—(24/06) T wave inversions in lead V2 and V6.

  • Bilateral (B/L) lower limb compression scan—negative.

  • Chest X-ray—B/L chest infiltrates.

  • High-resolution computed tomography (CT) chest (outside report)—B/L ground glass opacities with patchy consolidation (Tables 1 to 3).

Table 1: Shows complete hemogram, electrolytes, and renal function test lab values
Lab investigations
Parameters 28/5 1/6 6/6 10/6 16/6 21/6 24/6 25/6 26/6
Hb 13 14 12.7 12 14.1 12.8 11 10.5 10.7
TLC 11,000 15,000 14,000 14,600 22,600 4,500 22,600 25,500 27,600
DLC N95 L1.7 N94 L1 N94 L2 N84 L6 N92 L2.5 N97 L6 N96 L02
Patelets (lakhs) 2.45 1.91 1.03 55000 3.54 2.7 1.8 2.11 2.18
Urea 29 38 31 56 55 20 19 26 59.9
Creatinine 0.5 0.8 0.4 0.4 0.3 0.5 0.4 0.6 1.02
Sodium 135 135 137 141 135 141 125 128 123
Potassium 3.6 4.8 3.8 5.4 4.9 5.5 4.1 5.4 5.9
Table 2: Highlights biochemical parameters and coagulation profile
Lab investigations: biochemistry
Parameters 28/5 1/6 6/6 10/6 16/6 21/6 24/6 25/6 26/6
T Bilrubin 0.8 0.7 0.4 0.5 0.2 0.32
SGDT 53 78 77 168 266 137 53 59.2
SGPT 97 119 87 158 356 265 322 86.5
Alkaline phosphate 194 279 410 308 102 476
Protien/Alb 5.8/2.8 6.5/3.5 6.5/1.9 4.8/2 5/2.1 6.39/1.8
CRP 38 28 128 151 10.7 103 141.1
Ferritin 1165 1792 1708 1023 1800
D-dimer 547 828 1080 1252 1561 25000
Procalcitonin 0.07 0.112 0.6 2.05 0.26 3.86
Table 3: Detailed acid blood gas analysis and SpO2 values
ABG 1/6 3/6 7/6 10/6 11/6 13/6 17/6 21/6 23/6 24/6 25/6
Potential of hydrogen 7.4 7.33 7.38 7.2 7.4 7.3 7.4 7.4 7.37 7.11 7.039
PCO2 43.6 57.7 49.5 92.5 53.4 57.2 44.3 43.5 47.7 74.1 109
PO2 68.2 67 63.6 62.5 49.3 65.2 77.2 68.3 66.6 51.4 54.7
SpO2 92.5 91.8 91.8 87 86.3 92 95.8 93.9 92.3 72.7 70.8
Bicarbonate 29.6 30.4 29.0 39.9 34 32.1 28.6 27.6 27 23.2 28.7
FiO2 0.7 0.8 0.6 0.6 0.8 0.5 0.7 0.5 0.8 0.9 0.9
PO2/FiO2 97.4 83 106 104 61 130.4 110.2 136.6 83.25 57 59


The patient was admitted with a history of fever and cough with shortness of breath with a rapid antigen test done outside for coronavirus disease 2019 (COVID-19), which was positive. The patient was on home isolation till 23rd May 2021, after which there was worsening of symptoms, and was admitted to a private hospital. The patient was desaturating with hypoxemia, for which he was given an injection. Dexamethasone and remidisvir injections for the next 5 days; however, due to worsening symptoms, the patient was referred to the Postgraduate Institute of Medical Education and Research (PGIMER) on 28th May 2021 in a medical emergency. He was put on V/CMV mode of ventilation within 6 hours of admission to PGIMER. Dexamethasone injection was continued for another 10 days, along with low molecular weight heparin (LMWH) and piptaz injection. On 1st July 2021 patient started having high-grade fever along with purulent secretions in the ET aspirates, which on culture showed growth of Pseudomonas aeruginosa, which was sensitive to cefoperazone/sulbactam. The bronchoscopy was performed, and BAL fluid sent for culture showed growth of Acinetobacter baumannii and Aspergillus. Hence, the patient was started on colistin, voriconazole, and methylprednisolone injection. After 2–3 days, the patient started having symptoms of hepatitis with raised liver enzymes, due to which voriconazole was stopped. Subsequently patient had a worsening course, and on 16th July 2021 patient started developing features of shock which were nonresponsive to fluids; hence vasopressors were started. Initially, noradrenaline was started; however, the BP was still below 65 mm Hg, for which he was given vasopressin. Contemplating the second episode of ventilator-associated pneumonia (VAP) again, an ET aspirate was sent, which grew Acinetobacter baumannii and Stenotrophomonas maltophilia. During this course patient also developed a few oral ulcers and complaints of diarrhea. The Tzank smear for oral ulcers was sent, which showed the presence of acanthocytes. With this, a suspicion of CMV and herpes simplex virus (HSV) was considered, and a serum DNA sample for CMV PCR was sent. With this suspicion, the patient was subsequently started on ganciclovir injection on 20th June 2021, ceftazidime injection (sensitive to Stenotrophomonas maltophilia), and teicoplanin injection (the report of CMV PCR was received post demise as 17,000 copies of CMV).

The patient had a worsening course and suffered from refractory shock even with dual inotropes though nonresponsive. As the patient was not being given steroids for the past 4–5 days, a secondary Adrenal insufficiency was contemplated in a COVID-19 setup, for which the patient was started on hydrocortisone and fludrocortisone on 24th July 2022. However, the BP continued to be less, with a mean arterial pressure of <65 mm Hg. The patient was in a fibrotic phase of ARDS with recurrent polymicrobial infections with poor response to antibiotics and antivirals and refractory shock; he succumbed to his illness succumbed on 26th June 2021.

Final Clinical Diagnosis

  • Diabetes mellitus (DM) type 2.

  • Severe COVID-19 ARDS.

  • Ventilator-associated pneumonia (VAP) recurrent—polymicrobial–bacterial-pseudomonas/Acinetobacter baumannii/Stenotrophomonas maltophilia with??Aspergillus.

  • Thrombocytopenia: Disseminated intravascular coagulation >heparin-induced thrombocytopenia

  • Disseminated CMV (hepatitis, diarrhea, pneumonia): Reactivation.

  • Secondary adrenal insufficiency.

  • Pulmonary thromboembolism.

  • Acute coronary syndrome.

Cause of death: Refractory septic shock.


Prof S Jain: Thank you, Dr Neeraj, for a detailed discussion. He has covered most of the factors which were there in this patient, primarily the cause of death due to polymicrobial infection. But Dr Neeraj, you have not covered the changes of COVID-19, that we are in the organizing phase of ARDS or possibly the fibrotic phase, so we are likely to see fibrotic COVID-19 with some amount of pulmonary thromboembolism which is possibly a part of COVID-19 disease.

Dr Neeraj: Definitely, sir, because the patient was having recurrent episodes of VAP and the other coexistent CMV infections, so we were not able to ventilate the patient as I have shown in the slides.

Prof S Jain: It is okay and alright. Let me read out a few comments. Dr Atul thinks it’s primarily CMV, Dr Nipun believes that liver involvement is because of COVID-19 or drugs. Dr Karthik believes in organizing pneumonia. Now the issue is the fungal infection of the lungs. You know to diagnose fungus, people have been commenting on the antibodies. Galactomannan, either done on the BAL, is more important than done in the serum. Primarily I don’t think there is jugglery, but whether it’s a single infection, dual infection, or a triple infection that is the virus, fungus or bacteria, or a combination of three, at what phases or are just a combination, or we are missing out something else like tuberculosis and so on. We have intensivist Dr Inderpal here with us. What would you like to say?

Dr Inderpal: This patient was primarily managed by our team in the hepatology ICU in nonhemolytic enterotoxin. Throughout the course, he required prone ventilation, so that is something that has to be added, and the way his lung compliance fell, it was rapid. We have seen in COVID-19 patients that compliance in some patients would be the same, but in this, it fell rapidly, so much so that we had to prone him throughout his course of illness. Methylprednisolone was started because of persistent ARDS as per the policy followed in the respiratory ICU. This patient did not fulfil the criteria of invasive Aspergillosis; that is, the antimicrobial stewardship program ICU modified the criteria because there was no resurgence of fever; he did not have any hemoptysis, so he was not fulfilling more than one criterion. So we attributed the isolation of Aspergillus to colonization, which was subsequently proved by multiple negative cultures of fungus in ET aspirate. I think Dr Neeraj has covered most of the things. If we find Aspergillus, it would be terminal rather than being there for a long time.

Prof S Jain: Alright, we have to see before we make a comment on many of the infections which cannot be diagnosed. Dr Nidhi, would you like to say that X-ray? Do they really help? CT, if it really helps or if it’s either a single infection or multiple?

Dr Nidhi: They help to some extent. For example, in this patient, we could see there was some coinfection along with COVID-19 pneumonia. COVID-19 pneumonia has typical phases, 0–4 days early stage, then till 8 days progressive stage, then peak stage till 13 days, then after 14 days, there is resolution. If we do not see this resolution, then either the patient has gone into ARDS, or there is some coinfection. There were some asymmetrical opacities that suggested coinfection, but we cannot differentiate between fungal or bacterial. If we had found some cavitation, we would have been more sure of fungal etiology. CT definitely would have helped. But there are no specific features to suggest fungally.

Prof S Jain: Yes, the important aspect is CMV, you know, COVID-19 and CMV. Two viral infections in the same. Possibly COVID-19 producing lymphocytotoxicity. On top of it, steroids are being given to the patient and ICU setting. So perfect setting for CMV reactivation.

Dr Inderpal: Cytomegalovirus (CMV) reactivation is seen commonly in critically ill patients. One has to keep a very high clinical suspicion which we were keeping in this patient because he had cytopenias which were new onset, and he developed liver involvement. Hence, we empirically started anti-CMV therapy in this patient, and subsequently, we were proven right.

Prof S Jain: Yes, (reading comments) we have Dr Behera, who is stressing the importance of CT chest, and Dr Puri talking about polymicrobial infection due to immunosuppression and damage to lungs and also some vascular events. With this, now, I have the privilege to invite Dr Suvradeep Mitra to present the autopsy findings.


Good morning, everyone.

A partial autopsy was performed on this patient, and the brain was not examined. The prosecutor noted that the pleural cavities yielded 300 mL of serous fluid on each side, whereas pericardial and peritoneal cavities were WNL.


Bilateral (B/L) lungs together weighed 950 gm. The anterior aspect showed thick fibrinous tags adherent to the chest wall in the left lung (Fig. 1A). Pleural aspect was shiny and showed patchy areas of opacification. The cut surface did not reveal any focal lesion or nodularity (Fig. 1B). There was diffuse consolidation and the lungs were firm to feel. No significant hilar or carinal lymphadenopathy was noted. The tracheobronchial tree showed focal areas of ulceration. Microscopy-lung showed various stages of diffuse alveolar damage. In a small patch of the lung, there were exudative type changes in the form of hyaline membrane formation (Figs 1C and D), fibrin ball within alveoli (Fig. 2B), Masson’s body formation, type 1 pneumocyte necrosis and type 2 hyperplasia with two types of mucinous metaplasia and squamous metaplasia (Figs 2C and D). The majority of lung parenchyma showed features of organization in the form of fibroblast and myofibroblast proliferation (Figs 3A and B). A few places also showed organizing pneumonia patterns with the formation of fibroblastic plugs within alveolar spaces. A few patchy areas also showed fibrotic areas with deposition of elastic tissue within these fibrotic areas. However, no definite honeycombing pattern was noted. Vascular changes in the form of fibrocellular intimal thickening and recanalizing thrombi in the pulmonary artery were also noted (Figs 3C and D). The COVID-19 immunohistochemistry (IHC) and COVID-19 PCR from fresh lung tissue came negative. (Courtesy: Dr Mini from Virology Department). However, postmortem serum samples taken at the time of autopsy showed severe acute respiratory syndrome coronavirus 2 positivity. Pleuritis was also noted with focal areas of bronchopneumonia. However, no Aspergillus, mucormycosis, or bacteria was highlighted on special stains. Occasional large cells with inclusion like nucleolus were also noted, suggesting CMV inclusion (Fig. 2A). However, IHC for CMV and PCR turned out negative.

Figs 1A to D: (A) Pleural surface shows thick fibrinous tags adherent to underlying lungs with a firm consistency; (B) Cut surface of the lungs showing diffuse consolidation; (C) Exudative phase of ARDS: focal areas of hyaline membrane formation; (D) Martius scarlet blue stain highlights hyaline membrane as red color

Figs 2A to D: (A) Type 2 pneumocyte hyperplasia with occasional large ones with prominent nucleoli (inset); (B) Focal areas show fibrin ball formation within alveoli; (C) Areas of mucinous metaplasia; (D) Squamous metaplasia with interstitial inflammation

Figs 3A to D: Organizing phase of ARDS: (A) Diffuse changes within interstitial fibrosis showing fibroblasts and myofibroblast proliferation; (B) Formation fibroblasts plugs within the alveolar spaces; (C) Pulmonary artery fibrocellular intimal thickening; (D) Recanalizing thrombus suggesting PAH


It weighed 1200 gm. The capsular surface did not show any nodularity, and occasional capsular wrinkling and mild mottling were noted (Fig. 4A). Biliary tree, portal vein, and splenic vein were normal. Microscopy showed distortion of lobular architecture by bridging septa formation (Fig. 4B). There is an approximation of portal tracts with central vein and focal area of inflammation within portal tracts (Fig. 4C). Occasional focus of azonal macrovesicular steatosis was noted. Occasional fibrin thrombi in sinusoids and portal venous radicals were also noted. HBsAg and hepatitis B core antigen IHC were negative. COVID-19 PCR also turned out to be negative (Fig. 4D).

Figs 4A to D: Liver: (A) Gross photograph of liver, spleen and pancreas complex showing firm liver with exaggerated mottling; (B) Distortion of lobular architecture by bridging septa formation highlighted on Masson’s trichrome stain; (C) Occasional focus of portal and lobular lymphocytic inflammation; (D) Negative IHC for hepatitis surface and core antigen

The spleen and pancreas were grossly and microscopically unremarkable.


It weighed 320 gm. The arch of the aorta showed complicated atherosclerosis (Fig. 5A). Coronaries arteries were dissected and showed a maximum of 25% of wall thickening. The heart was open with the four-chamber method and showed left ventricular hypertrophy with right ventricle and right atrial dilatation. Microscopically heart was unremarkable, and no venulitis or myocyte injury was noted (Fig. 5B). The COVID-19 reverse transcription (RT-PCR) was negative.

Figs 5A to E: (A) Gross heart-left ventricular hypertrophy with dilatation of right ventricle and atrium; (B) Complicated atherosclerosis in the arch of aorta; (C) Heart, microscopically unremarkable; (D) Gross kidney: capsular surface shows depressed cortical scars, cut surface showed distinct CM junction; (E) Micro focal changes of benign nephrosclerosis were noted (arrow)


Although, it weighed 200 gm. The renal artery and Ostia were patents (Fig. 5C). There were depressed renal scars over the cortical surface; however, the corticomedullary (CM) junction was distinct. The microscopy-glomerular compartment was relatively preserved, but Masson’s trichrome stain highlighted focal interstitial fibrosis and tubular atrophy. Changes of benign nephrosclerosis with medial hypertrophy of the medium-sized arteries and cast nephropathy were also noted (Fig. 5D).

  • The adrenal gland did not show any CMV inclusion.

  • The stomach, esophagus, small intestine, and large intestine did not show any ulceration and were microscopically unremarkable.

  • Testis showed atrophic changes with Leydig cell hyperplasia.

  • Thyroid and parathyroid were unremarkable.

  • Bone marrow showed normal trilineage hematopoiesis.


A 58-year-old male, hypertensive, and recently diagnosed with type 2 DM post-COVID-19 ARDS:

Thank You.


Prof Jain: Thank you, Dr Mitra. Now we have the pathological and clinical details of this patient in front of you, and there are a few points that would need a little bit of clarification. Dr Mitra, you did mention IHC was positive, but the RT-PCR was negative.

Dr Mitra: No, sir IHC was negative.

Dr Jain: Okay, it was negative. Do you believe that we should be doing IHC, or should we be doing RT-PCR because doing IHC is easier? I thought

Dr Mitra: Yes, but the positivity of IHC is difficult to interpret, and it is often focal and comes in the exudative phase only. However, when we see such kind of organizing phase or late phase of ARDS, the IHC can turn out to be negative. So RT-PCR could be better in that scenario.

Prof Jain: No, I am saying this because in other organs also, you can do it in the liver, spleen, kidneys, heart and so on to look at the extrapulmonary COVID-19. Now, what about the infections? Would Dr Inderpal like to comment on it? You know, picking up bacteria on a gram stain or, you know, all these morphologically is difficult. We believe much more in cultures, antigen detection and so on.

Dr Inderpal: I think there was definitely evidence of bronchopneumonia and we had culture positivity for bugs which primarily were being treated. Why we could not find CMV is that perhaps he has been treated with ganciclovir and he has received at least 2 weeks of ganciclovir. So I assume that is why we have not seen CMV floridly involving multiple organs. Had we not treated, perhaps you would have seen, so that is one thing. Why has he died? Because he had progressive fibrosis. I don’t think extracorporeal membrane oxygenation (ECMO) or transplant is the answer. In our setting, we can’t do it even normally. I mean, in COVID-19 patients, it’s not possible. So he had diffuse lung damage and diffused alveolar damage. My only question is, did he have acute fibrinous organizing pneumonia? Because you have shown fibrinous balls, you have shown fibrosis and organizing pneumonia.

Dr S Mitra: Sir, when we label it as acute fibrinous and organizing pneumonia (AFOP), we have to rule out any evidence of hyaline membrane disease, so if you have an AFOP pattern with hyaline membrane, we should always label it as diffuse alveolar lung damage

Prof S Jain: Okay. I mean just wanted to know, for lung transplant do we need COVID-19 negativity?

Dr Inderpal: Obviously, we need COVID-19 negativity because if it is still involving the lung, nobody is going to open up the patient. But the kind of involvement this patient had, probably, I don’t think much would have made the difference.

Prof S Jain: Yes, many times, ECMO would have been a bridging thing, and it would have bought time.

Dr Inderpal: But this patient had already gone into the fibrotic phase, although he did not develop honeycombing.

Prof S Jain: I know that just maintaining these patients on either ventilation or ECMO wouldn’t be the answer. The final answer would be transplanted, but unless we offer it, we can give time for the lung to heal.

Dr Inderpal: If you want the lung transplant to be successful, generally, it is successful in patients who are mobile, whom you are able to mobilize. In a patient who has been critically ill for almost 1 month on a ventilator, I don’t think that even a lung transplant at this stage would have really helped. More so, given the fact that he had multiple infections also. So we should take into account everything.

Prof S Jain: Yes, I know, he is a borderline type of age with other comorbidities and so on.

Dr Inderpal: A patient who is young and comes with acute interstitial pneumonia, which also has a very high mortality, and he was otherwise normal. So perhaps, there, one would think of a lung transplant earlier in the disease course rather than waiting for a month to worsen, and the patient builds up nutritionally and also gets depleted. So it’s difficult to do a transplant in such a setting.

Prof S Jain: Coming on to the liver. Nipun believes that it could be vascular or ischemic. What do you say about liver injury? Is it a virus or a drug?

Dr S Mitra: Yes, sir, it is very difficult to say, sir, but I believe that viral aetiology would have played a role in it.

Prof S Jain: Very unlikely to be ischemic because that involves the centrizonal areas.

Dr S Mitra: I feel viruses and drugs are the most common causes.

Prof S Jain: Yes, Dr Neeraj, would you like to say anything else? Are you happy with the pathology shown or something?

Dr Neeraj: Sir, I think we have got a good clinicopathological correlation, Viremia was there, and the sample was sent earlier and as discussed ganciclovir was given for 2 weeks, so that could be the reason we couldn’t find the CMV virus in autopsy.

Prof S Jain: Still, within 2 weeks, you thought that the virus would clear off? I doubt very much that it would clear off. Good works are that since the fireworks are banned, we didn’t have fireworks today.

Dr Inderpal: Sir, I would like to highlight another fact isolating Aspergillus from the respiratory tract in the absence of supporting evidence or fulfilling criteria, we should not loosely label these patients as corrective and preventive actions (CAPA) or invasive Aspergillosis and wrongly treat them. As we have seen in this case today. We need to have good definitions. If we have the criteria, we should follow them rather than labelling them as CAPA, otherwise, there would be falsely high values of fungal infections in our settings.

Prof S Jain: Yes, thank you, everybody, and I wish you all a very happy and pleasant Diwali. Keep safe.


A 58-year-old male with a fever for 10 days associated with dry cough and shortness of breath for 5 days turned out to be COVID-19 positive and kept in isolation and symptomatic treatment. After 15 days of onset of symptoms, he developed respiratory distress having tachypnea with hypoxemia and was treated with dexamethasone and remdesivir injection for 5 days at a private hospital. Due to worsening symptoms, he was referred to PGIMER and continued to have the same treatment along with LMWH and piptaz injections. He developed a high-grade fever after 3 days with purulent secretions with ET aspirate growth of Pseudomonas aeruginosa sensitive to cefoperazone/sulbactam. The BAL fluid also showed growth of Acinetobacter baumannii and Aspergillus. Hence, it was started on colistin, voriconazole, and methylprednisolone injections. After 2–3 days, he had symptoms of hepatitis with raised liver enzymes, due to which voriconazole was stopped. Subsequently patient had a worsening course with refractory shock nonresponsive to fluids and vasopressors. His Tzank smear for oral ulcers showed the presence of acanthocytes with suspicion of CMV and HSV, and he started on ganciclovir injection on 20th June 2021, ceftazidime (sensitive to Stenotrophomonas maltophilia) and teicoplanin injections. His lab parameters were significantly deranged, including raised liver enzymes with positive D-Dimer and significantly high CRP. The patient succumbed to his illness on 26th June 2021.

The pathology revealed both exudative and organizing phases of ARDS with hyaline membrane formation and extensive loss of type 1 pneumocytes and proliferation of type 2 pneumocytes with mucinous and squamous metaplasia. In addition, there were areas of interstitial inflammation and fibrosis suggesting organization (fibrotic phase) of ARDS with changes of pulmonary arterial hypertension (PAH) though lacking honeycombing. However, in spite of significant copies of CMV, none of the organs revealed a classical CMV inclusion, possibly due to adequate antiviral treatment.

The ARDS is reported to be 42% in patients with COVID-19 pneumonia, requiring intensive care. COVID-19 ARDS follows a median time of 8.5 days after symptom onset, which was almost double in the index case. Thus, it is pertinent to monitor such patients for the development of ARDS as the infection progresses through RT-PCR may be negative for COVID-19 even in the tissues. RR and SpO2 are the most important parameters for a clinical assessment for early recognition of ARDS. In addition, the development of superadded polymicrobial infections needs to be monitored and treated in time to reduce mortality.

This patient highlights the immune response generated in a COVID-19 setup in spite of the best available timely treatment of COVID-19 complications in a pandemic setting. Though he truly was not immunosuppressed, as the diabetes was of very recent onset, however, it might have played a significant role in his immune reaction and treatment response.

This case teaches us that even if the patient is treated in the best-of-care hospital, the lung involvement is sufficient enough for the demise of the patient with superadded polymicrobial infections in a COVID-19 setup.

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