Coronavirus

How common is hyponatremia in patients with Covid-19 and what’s its significance?  

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , Leave a comment

Hyponatremia has been reported between 20% and 35% of patients hospitalized for Covid-19, 1-5 with low serum sodium levels on admission often associated with progression to severe illness, mechanical ventilation, increased length of stay and death.1,2,4,5

A 2023 retrospective multicenter study involving over 2,600 hospitalized Covid-19 patients (between February 2020 and August 2022) found hyponatremia in 34.2%: Mild (Na 131-134 mmol/L) 25.1%, moderate (Na 126-130 mmol/L) 7.5% and severe (<126 mmol/L) 1.8%.3 There was a significant association between male sex at birth, hypertension, chronic kidney disease, immunosuppressives, thiazide diuretics and hyponatremia.3

Similarly, another retrospective study of hospitalized Covid-19 patients found an association between hyponatremia and several common chronic diseases, such as diabetes, hypertension, ischemic heart disease, chronic liver disease and chronic kidney disease.4 It’s important to note that since older age has also been found to be a risk factor for hyponatremia in Covid-19, the independent contribution of these conditions to hyponatremia is unclear.3

As with many other infectious diseases, the mechanism of hyponatremia in patients with Covid-19 likely has multiple causes, including hypovolemia, syndrome of inappropriate anti-diuretic hormone secretion (SIADH), diuretic use and corticosteroid deficiency, particularly in the critically ill. 1-4  

Interestingly, a study performed early in the pandemic (March 2020) found that the majority (57%)  of hospitalized Covid-19 patients with hyponatremic were euvolemic and that the administration of isotonic saline to such patients was independently associated with increased hospital mortality (cause unclear).2 The authors suggested closer attention to the volume status of Covid-19 patients with hyponatremia (eg, through closer attention to the jugular venous pressure on physical exam) before considering treatment with isotonic saline.

Last, Covid-19 may be associated with hyponatremia during the post-discharge period as well.  An intriguing 2024 study found nearly 25% of patients with Covid-19 developed hyponatremia (<135 mmol/L) during the 1-year follow-up period after discharge with most not reported to have hyponatremia during their index hospitalization.5 In the same study, hyponatremia was associated with older age, male sex, diabetes, hypertension, heart failure, previous invasive ventilatory support and increased rate of readmission.5

Bonus Pearl: Did you know that there is an inverse relationship between interleukin-6, a key pro-inflammatory cytokine, and plasma sodium levels in Covid-19 and that this association may be stronger than that of other viral or bacterial respiratory infections?2  

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References

  1. Ayus JC, Klantar-Zadeh K, Tantisattamo E, et al. Is hyponatremia a novel marker of inflammation in patients with Covid-19? Nephrol Dial Transplant 2023;38:1921-24. Is hyponatremia a novel marker of inflammation in patients with COVID-19? – PubMed (nih.gov)
  2. Pazos-Guerra M, Ruiz-Sanchez JG, Perez-Candel X, et al. Inappropriate therapy of euvolemic hyponatremia, the most frequent type of hyponatremia in SARS-CoV-2 infection, is associated with increased mortality in COVID-19 patients. Front Endocrinol 2023; 14:1227058. Inappropriate therapy of euvolemic hyponatremia, the most frequent type of hyponatremia in SARS-CoV-2 infection, is associated with increased mortality in COVID-19 patients – PubMed (nih.gov)
  3. De Haan L, ten Wolde, Beudel M, et al. What is the aetiology of dynatreaemia in COVID-19 and how is this related to outcomes in patients admitted during earlier and later COVID-19 waves? A multicentre, restrospective observational study in 11 Dutch hospitals. BMJ Open 2023;13:e075232. Original research: What is the aetiology of dysnatraemia in COVID-19 and how is this related to outcomes in patients admitted during earlier and later COVID-19 waves? A multicentre, retrospective observational study in 11 Dutch hospitals – PMC (nih.gov)
  4. Rehman F, Rehan ST, Rind BJ, et al. Hyponatremia causing factors and its association with disease severity and length of stay in Covid-19 patients: A retrospective study from tertiary care hospital. Medicine 2023; 102:45(e35920) Hyponatremia causing factors and its association with disease severity and length of stay in COVID-19 patients: A retrospective study from tertiary care hospital – PubMed (nih.gov)
  5. Biagetti B, Sanchez-Montalva A, Puig-Perez A, et al. Hyponatremia after COVID-19 is frequent in the first year and increases re-admissions. Scientific Reports 2024:14:595. Hyponatremia after COVID-19 is frequent in the first year and increases re-admissions – PubMed (nih.gov)

 

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

How common is hyponatremia in patients with Covid-19 and what’s its significance?  

My patient with Covid-19-related generalized weakness has rhabdomyolysis. How common is rhabdomyolysis in Covid-19?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , Leave a comment

Covid-19-associated rhabdomyolysis has been reported since the early years of the pandemic with an overall prevalence ranging from 4%-20% among hospitalized patients and nearly 50% in ICU patients.1-5

In a 2023 scoping review of Covid-19-associated rhabdomyolysis involving 117 cases (January 2020-July 2022),1 68.4% had at least one reported non-Covid-19 risk factor (excluding hypoxemia), including age 65 years or older, metabolic syndrome features, hypothyroidism, previous rhabdomyolysis, hemoglobinopathy, trauma/compression or selected rhabdomyolysis-associated medications.  Presenting symptoms did not always include myalgias or weakness with some patients only presenting with fever, back pain, respiratory symptoms, or fatigue. Mortality was high (32% and 21% in those with or without other risk factors, respectively).  Routine creatine kinase (CK) testing was suggested for hospitalized patients with a low threshold for testing outpatients with Covid-19.

A 2024 cross-sectional study involving hospitalized Covid-19-patients (March 2020-March 2021) reported the following independent factors for concurrent rhabdomyolysis: male gender, dyspnea, hyponatremia, myalgia, elevated D-dimer, aspartate transaminase-AST (3x higher than normal) and platelet count >450,000 (cells/L).2 In the same study, myalgia was reported in only 30% of patients with rhabdomyolysis.   

Potential mechanisms explaining the association between Covid-19 and rhabdomyolysis include hypoxemia, viral myositis (either directly or immune-mediated), viral-induced mitochondrial dysfunction, cytokine storm, hypovolemia and Covid-related coagulopathies.1,2,4

Bonus Pearl: Did you know that although the 3 most common symptoms of patients with rhabdomyolysis are myalgias, muscle weakness and dark urine, the triad is present in only 10% of patients? 6

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References

  1. Preger A, Wei R, Berg B, et al. Covid-19-associated rhabomyolysis: A scoping review. Intern J Infect Dis 2023:136:115-126. COVID-19-associated rhabdomyolysis: A scoping review – PubMed (nih.gov)
  2. Hashemi B, Farhangi N, Toloul A, et al. Prevalence and predictive factors of rhabydomyolysis in Covid-19 patients: A cross-sectional study. Indian J of Nephrol 2024;34:144-48. Prevalence and Predictive Factors of Rhabdomyolysis in COVID-19 Patients: A Cross-sectional Study – PubMed (nih.gov)
  3. Samardzic T, Muradashvill T, Guirguis S, et al. Relationship between rhabdomyolysis and SARS-CoV-2 disease severity. Cureus 16:e53029 (January 27, 2024). Relationship Between Rhabdomyolysis and SARS-CoV-2 Disease Severity – PubMed (nih.gov)
  4. Haroun MW, Dielev V, Kang J, et al. Rhabdomyolysis in Covid-19 patients: A retrospective observational study. Cureus 13:e12552. Rhabdomyolysis in COVID-19 Patients: A Retrospective Observational Study – PubMed (nih.gov)
  5. Albaba I, Chopra A, Al-Tarbsheh AH, et al. Incidence, risk factors, and outcomes of rhabdomyolysis in hospitalized patients with Covid-19 infection. Cureus 13:e19802. Incidence, Risk Factors, and Outcomes of Rhabdomyolysis in Hospitalized Patients With COVID-19 Infection – PubMed (nih.gov)
  6. Lu W, Li X, You W, et al. Rhabdomyolysis in a patient with end-stage renal disease and SARS-CoV-2 infection: A case report. Medicine 2023;102:48(e36360). Rhabdomyolysis in a patient with end-stage renal disease and SARS-CoV-2 infection: A case report – PMC (nih.gov)

 

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

My patient with Covid-19-related generalized weakness has rhabdomyolysis. How common is rhabdomyolysis in Covid-19?

Is there an association between Covid-19 and subsequent development of hypertension?

FA Manian MD, MPH, , , , , , , , , , , , Leave a comment

Although far from definite, emerging evidence suggests that adults with recently diagnosed Covid-19 are at increased risk of newly-diagnosed hypertension following the acute infection.1-4

A retrospective cohort study involving a large national healthcare data base of the Department of Veterans Affairs found that, at a median follow-up of 126 days, Covid-19 survivors had an excess burden of newly-diagnosed hypertension (15/1000 patients) and were at higher risk of initiation of antihypertensive drugs compared to controls.2

Another retrospective cohort study involving over 80,000 adults 65 years or older (median follow-up 56 days) found an increased risk of newly-diagnosed hypertension (O.R. 4.4; 95% C.I. 2.27-6.37) in the Covid-19 group. 3  Even in a younger population (18-65 years of age), the same investigators found a significant increase (81%; 95% C.I. 10-196%) in the risk of newly diagnosed hypertension in the Covid-19 group compared to that of the control cohort. 4  

Despite the inherent limitations in these retrospective studies, a cause-and-effect relationship between Covid-19 and subsequent diagnosis of hypertension is plausible given the known affinity of SARS-CoV-2 for ACE2 receptors and endothelial cells. 5   Of interest, hyperreninemia associated with reduced glomerular filtration rate has been reported in some patients with Covid-19 requiring prolonged intensive care. 6

Bonus Pearl: Did you know that Covid-19 survivors have also been reported to have an increased risk of stroke, transient ischemic attack, ischemic heart disease, pericarditis, myocarditis, heart failure, dysrhythmia, and thromboembolic disease, independently of pre-existing hypertension and other cardiovascular risk factors? 7

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References

  1. Shibata S, Kobayashi K, Tanaka M, et al. Covid-19 pandemic and hypertension: an updated report from the Japanese Society of Hypertension project team on Covid-19. Hypertens Res 2022 Dec 23:1-12. COVID-19 pandemic and hypertension: an updated report from the Japanese Society of Hypertension project team on COVID-19 – PMC (nih.gov)
  2. Al-Aly Z, Xie Y, Bowe B. High-dimensional characterization of post-acute sequelae of Covid-19. Nature 2021;594:259-64. High-dimensional characterization of post-acute sequelae of COVID-19 – PubMed (nih.gov)
  3. Daugherty SE, Guo Y, Health K, et al. Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study. BMJ 2021;373:n1098. Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study | The BMJ
  4. Guney C, Akar F. Epithelial and endothelial expressions of ACE2:SARS-CoV-2 Entry Routes.  J Pharm Pharm Sci 2021;24:84-98 Epithelial and Endothelial Expressions of ACE2: SARS-CoV-2 Entry Routes – PubMed (nih.gov)
  5. Cohen K, Ren S, Health K, et al. Risk of persistent and new clinical sequelae among adults aged 65 years and older during the post-acute phase of SARS-CoV-2 infection: retrospective cohort study. BBMJ 2022;376:e068414. Risk of persistent and new clinical sequelae among adults aged 65 years and older during the post-acute phase of SARS-CoV-2 infection: retrospective cohort study – PubMed (nih.gov) 
  6. Hulstom M, von Seth M, Frithiof R. Hyperreninemia and low total body water may contribute to acute kidney injury in coronavirus disease 2019 patients in intensive care. J Hypertens 2020 May 28. Hyperreninemia and low total body water may contribute to acute kidney injury in corona virus disease 2019 patients in intensive care – PMC (nih.gov)
  7. Xie Y, Xu E, Bowe B, et al. Long-term cardiovascular outcomes of Covid-19. Nat med 2022;28:583-90. Long-term cardiovascular outcomes of COVID-19 – PMC (nih.gov)

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Is there an association between Covid-19 and subsequent development of hypertension?

Is loss of sense of smell or taste much less common in Omicron-related Covid-19 compared to earlier strains of SARS-CoV-2?

FA Manian MD, MPH, , , , , , , , , , , , Leave a comment

Absolutely! Although loss of smell was a cardinal symptom of Covid-19 with earlier strains of SARS-CoV-2 (eg, Wuhan, alpha, delta), on average omicron causes olfactory dysfunction in only 13% of patients, 3-4 times lower than the earlier strains.1

But why is omicron less likely to causes loss of smell or taste? There may be at least 2 explanations. First explanation revolves around the solubility of omicron in the olfactory mucus. Recall that to access the olfactory epithelium, viruses and other pathogens have to first dissolve in and penetrate the mucus layer that not only allows odorants to reach the olfactory receptors but also protects the olfactory epithelium from toxins and pathogens. Hydrophilic and acid proteins can penetrate the mucus barrier more easily because they are more soluble in the mucus layer.1

What does this have to do with omicron? Well, it turns out that omicron with all its mutations in the spike protein is actually more alkaline than the Wuhan and delta strains. This means that omicron may have lower solubility in mucus and have a harder time reaching and infecting the olfactory epithelium. 1 Since the composition of olfactory mucous differs significantly from other mucus layers in the respiratory tract, omicron may still cause disease.2

Another potential mechanism may be related to the inefficiency of omicron in other steps necessary to infect nonneuronal cells of the olfactory epithelium within the nasal cavity, such as the endosomal route. 1 It turns out that cells of the olfactory epithelium express less of the endosomal membrane fusion proteases (cathepsins) which omicron prefers for cell entry! Fascinating! 

Bonus Pearl: Did you know that only 5-10% of functional olfactory neurons are required for a relatively normal sense of smell? This means that SARS-CoV-2 needs to eliminate at least 90% of all support cells of the olfactory neurons within a 3-4 day period (before their regeneration) for the host to notice anosmia?

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References

  1. Butowt R, Bilinska K, von Bartheld C. Why does the omicron variant largely spare olfactory function? Implications for the pathogenesis of anosmia in coronavirus disease 2019. J Infect Dis 2022;226:1304-1308. Why Does the Omicron Variant Largely Spare Olfactory Function? Implications for the Pathogenesis of Anosmia in Coronavirus Disease 2019 – PubMed (nih.gov)
  2. Yoshikawa K, Wang H, Jaen C, et al. The human olfactory cleft mucus proteome and its age-related changes. Sci Rep 2018;8:17170. The human olfactory cleft mucus proteome and its age-related changes – PMC (nih.gov)
  3. Harding JW, Getchell TV, Margolis FL. Degeneration of the primary olfactory pathway in mice. V. Long-term effect of intranasal ZNS04 irrigation on behavior, biochemistry and morphology. Brain Res 1978;140:271-85. Denervation of the primary olfactory pathway in mice. V. Long-term effect of intranasal ZnSO4 irrigation on behavior, biochemistry and morphology – PubMed (nih.gov)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Is loss of sense of smell or taste much less common in Omicron-related Covid-19 compared to earlier strains of SARS-CoV-2?

Why do some patients with Covid-19 develop a rebound after completing a course of Paxlovid (nirmatrelvir/ritonavir) and how common is it?

FA Manian MD, MPH, , , , , , Leave a comment

Covid-19 rebound, characterized by the recurrence of Covid-19 symptom or a new positive viral test after having tested negative, is a poorly understood phenomenon that can occur after completion of therapy with Paxlovid, Molnupiravir (another antiviral Covid-19 drug) and even in patients with acute Covid-19 who never received any specific antiviral therapy. 1-6

Based on very limited number of studies, it appears that rebound is not caused by emergence of drug resistance or absence of neutralizing immunity, rather resumption of SARS-CoV-2 replication following completion of therapy, triggering a secondary immune-mediated response that’s associated with clinical symptoms.2,3

Recent studies suggest that rebound following Paxlovid treatment may not be as common as one may think.  In a cohort of 483 high-risk patients treated with Paxlovid for Covid-19, 0.8% experienced rebound of symptoms within 30 days of diagnosis, which were generally mild at a median of 9 days after treatment, all resolving without additional antiviral therapy.3  In this study, the median age was 63 years and 93% were fully vaccinated; there were no hospitalization related to rebound or deaths. In another study (pre-print) involving over 11,000 patients treated with Paxlovid, rebound symptoms occurred in 2.3% and 5.9% of patients  7 and 30 days following therapy, respectively, with similar rates reported in patients treated with Molnupiravir.4

Interestingly, a preprint article involving 568 untreated patients with mild-moderate Covid-19 found that 27% had symptom rebound after initial improvement with 12% having viral rebound based on nasal swabs with ≥0.5 log viral RNA copies/ml. 5 So antiviral therapy for Covid-19 is not a prerequisite for rebound symptoms.

Although some have suggested that insufficient drug exposure either due to individual pharmacokinetics or insufficient duration may be the cause of rebound in treated patients,2   there is currently no evidence that additional treatment for Covid-19 is needed in these patients.6

Despite reports of rebound, Paxlovid should still be considered in selected patients with mild-moderate Covid-19 at high risk of complications to minimize the risk of hospitalization and death from Covid-19. 

Bonus Pearl: Did you know that, according to CDC, Covid-19 rebound often occurs between 2-8 days following initial recovery? 1

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References

  1. Covid-19 rebound after paxlovid treatment. May 24, 2022. COVID-19 Rebound After Paxlovid Treatment (cdc.gov)
  2. Carlin AF, Clark AE, Chaillon A, et al. Virologic and immunologic characterization of Coronavirus Disease 2019 recrudescence after nirmatrelvir/ritonavir treatment. Clin Infec Dis 2022 (June 20). Virologic and Immunologic Characterization of Coronavirus Disease 2019 Recrudescence After Nirmatrelvir/Ritonavir Treatment | Clinical Infectious Diseases | Oxford Academic (oup.com)
  3. Ranaganath N, O’Horo JC, Challner DW, et al. Rebound phenomenon after nirmatrelvir/ritonavir treatment of Coronavirus Disease-2019 in high-risk persons. Clin Infect Dis 2022 (June 14). https://doi.org/10.1093/cid/ciac481 Rebound Phenomenon after Nirmatrelvir/Ritonavir Treatment of Coronavirus Disease-2019 in High-Risk Persons | Clinical Infectious Diseases | Oxford Academic (oup.com)
  4. Wang L, Berger NA, David PB, et al. Covid-19 rebound after Paxlovid and Molnupiravir during January-June 2022. MedRxiv 2022. COVID-19 rebound after Paxlovid and Molnupiravir during January-June 2022 | medRxiv
  5. Deo R, Choudhary MC, Moser C, et al. Viral and symptom rebound in untreated Covid-19 infection. Medrxiv 2022. Viral and Symptom Rebound in Untreated COVID-19 Infection (medrxiv.org)
  6. Covid-19 rebound after Paxlovid treatment. May 24, 2022. HAN Archive – 00467 | Health Alert Network (HAN) (cdc.gov)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

 

Why do some patients with Covid-19 develop a rebound after completing a course of Paxlovid (nirmatrelvir/ritonavir) and how common is it?

What’s so “special” about SARS-CoV-2 Omicron subvariants BA.4 and BA.5?

FA Manian MD, MPH, , , , , , , , , , , , , , , , Leave a comment

BA.4 and BA.5 now account for the majority of Covid cases in the U.S.1  Several concerning features of BA.4 and BA.5 when compared to earlier strains of SARS-CoV-2 include:2-6

  1. High reproductive rate or R0 ie, the average number of new infections generated by an infectious person in a totally naïve population. BA.4/5 has an estimated R0 of 18.6, according to a one report.  For comparison, the R0 for the original Wuhan variant was estimated at 3.3, for Delta  5.1, early Omicron  9.5, BA.1 13.3, mumps 12, and measles 18.  So, it’s not surprising that we are currently experiencing higher rates of SARS-CoV-2 transmission in the population than just a few weeks ago.3
  2. Suboptimal existing immunity following prior infections due to Omicron variants BA.1 and BA.2, or prior vaccinations (including 3 doses of Pfizer vaccine).2,4
  3. More efficient spread than BA.2 when studied in human lung cells invitro. 2
  4. More pathogenic than BA.2 in hamsters. 2
  5. Reduced activity of SARS-CoV-2 therapeutic monoclonal antibodies.4
  6. Antigenically distant from other SARS-CoV-2 variants, with 50 mutations, including more than 30 on the spike protein, the viral protein targeted by Covid vaccines to induce immunity.5,6

Despite these potentially ominous traits, currently there is no evidence that  BA.4 or BA.5 is inherently more likely to cause severe disease than that caused by other Omicron subvariants.   The sheer number of infected persons in the population due to high transmission rates, however, will likely translate into higher hospitalization and deaths which has already happened in many areas.

High transmission rates also mean that we should not abandon the usual public health measures (eg, social distancing, masking indoors in public spaces) and vaccination with boosters for eligible persons with the aim of reducing hospitalization and death, if not infections.  

Bonus Pearl: Did you know that BA.4 and BA.5 became dominant in South Africa in April, 2022, despite 98% of the population reportedly having some antibodies from vaccination or previous infection or both?  

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References

  1. Leatherby L. What the BA.5 subvariant could mean for the United States. NY Times, July 7, 2022. https://theconversation.com/australia-is-heading-for-its-third-omicron-wave-heres-what-to-expect-from-ba-4-and-ba-5-185598
  2. Kimura I, Ymasoba D, Tamura T, et al. Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5. bioRxiv, preprint doi: https://doi.org/10.1101/2022.05.26.493539 , posted May 26, 2022. Accessed July, 13, 2022.
  3. Esterman D. The Conversation. Australia is heading for its third Omicron wave. Here’s what to expect from BA.4 and BA.5. July 4, 2022. https://theconversation.com/australia-is-heading-for-its-third-omicron-wave-heres-what-to-expect-from-ba-4-and-ba-5-185598
  4. Tuekprakhon A, Nutalai R, Dijokaite-Guraliuc A, et al. Antibody escape of SARS-COV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum.
  5. Katella K. Omicron and BA.5: A guide to what we know. YaleMedicine, July 6, 2022. https://www.yalemedicine.org/news/5-things-to-know-omicron
  6. Topol E. The BA.5 story. The takeover by this Omicron sub-variant is not pretty. Ground Truths. June 27, 2022. https://erictopol.substack.com/p/the-ba5-story

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What’s so “special” about SARS-CoV-2 Omicron subvariants BA.4 and BA.5?

What’s the latest on second Covid vaccine boosters and should I recommend them to my adult patients?

FA Manian MD, MPH, , , , , , , , , Leave a comment

On March 29, 2022, the CDC and the FDA approved second booster shots of Pfizer and Moderna Covid vaccines for everyone 50 years of age or older as well as people 12 years of age or older with moderate to severe immune deficiencies to be given at least 4 months following the first booster.1-3  This means a 4th dose of an mRNA vaccine for many adults and a 5th dose for those with moderate to severe immune deficiencies. 

Admittedly, these recommendations are made in the context of many uncertainties, including when the next Covid surge will arrive, what will be the predominant variant, and how will our immunity hold up if a surge occurs. 

Nevertheless, in discussing the merits of a 2nd booster, I would emphasize several “talking points”:

  • Covid hasn’t gone away with new cases still diagnosed daily, some still  requiring hospitalization, albeit at lower frequency than recent past. 
  • Our immunity against Covid wanes in the absence of boosters or natural infection.
  • SARS-CoV-2 has been unpredictable in its surges, as well as emergence of new variants with frequent changes in its virulence and ease of transmission. This means we don’t know when the next surge will hit us (summer, fall or later) and how the predominant variant will behave.
  • But let’s not get too hung up on surges! The fact is that as long as Covid is circulating around, maintaining a robust immunity against infection is the best way to avoid getting infected and the best way to do this is through boosters!
  • As more people go around without masks, the risk of unprotected exposure to SARS-CoV-2 is also likely to increase, particularly in indoor public gatherings.  Boosters may allow us the freedom to go maskless more often!
  • The risk of Long Covid even following mild infection is still real even between surges. This means even if we don’t get very sick from Covid, we are placing ourselves at risk of Long Covid. Remember, no Covid, no Long Covid!
  • Irrespective of whether it’s mild or even asymptomatic, Covid infection  can cause significant disruption in our lives, whether it be isolation at home, not being allowed to return to work or just the anxiety of having it or having passed it to others. This means that, at least currently, it’s premature to consider this virus as “just another respiratory virus.”  It’s impact on our everyday lives is still a lot different than typical respiratory viruses. 
  • mRNA vaccine boosters have been proven to be as safe as primary series. 
  • Last, but not the least, a preprint Israeli study involving volunteers 60 to 100 years old found a 78% reduction in mortality from Covid following a 2nd booster dose of Pfizer mRNA vaccine compared to those who only had 1 booster.4  This study has several limitations including self-selected volunteers who may already be at lower risk of Covid mortality due to their healthier lifestyle. Nevertheless, the data is very encouraging!

Ultimately, the decision to get a second booster, particularly during non-surge periods, will depend a lot on not only available facts but the individual’s threshold for acceptable risk of even mild disease, concern over transmission to others and more recently the cost of the vaccine, among other factors.  

Bonus Pearl: Did you know that each year there are plenty of uncertainties around which influenza A or B subtypes will be the predominant seasonal strain or what month they may surge but these questions never keep us from recommending the annual flu vaccine to the public as a means of reducing influenza cases and saving lives?   

 

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References

  1. D.A. Allows Second Covid Boosters for Everyone 50 and Older – The New York Times (nytimes.com)
  2. Coronavirus (COVID-19) Update: FDA Authorizes Second Booster Dose of Two COVID-19 Vaccines for Older and Immunocompromised Individuals | FDA
  3. CDC Recommends Additional Boosters for Certain Individuals | CDC Online Newsroom | CDC
  4. Arbel R, Sergienko R, Friger M, et al. Second booster vaccine and Covid-19 mortality in adults 60-100 years old. Preprint, posted March 24, 2022. 24514bba-2c9d-4add-9d8f-321f610ed199.pdf (researchsquare.com)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

What’s the latest on second Covid vaccine boosters and should I recommend them to my adult patients?

Should healthy adults receive a Covid vaccine booster shot and why?

FA Manian MD, MPH, , , , , , , , , Leave a comment

A booster shot of Covid vaccine (eg, mRNA, Pfizer or Moderna) is now recommended by the CDC even for healthy adults as follows:1

  • If you received Pfizer vaccine as your primary series, are ≥12 years old and at least 5 months after your 2nd dose
  • If you received Moderna vaccine as your primary series, are ≥18 years old and at least 5 months after your 2nd dose
  • If you received J&J vaccine, are ≥18 years old and at least 2 months after your 1st dose

There are at least 3 reasons for receiving a Covid vaccine booster: 1

  • Waning immunity after primary vaccine series
  • Emergence of Omicron variant which seems to be less responsive to the existing immunity from the vaccine
  • Recent data from clinical trials showing that a booster shot increased the immune response in trial participants who completed an either Pfizer or Moderna mRNA vaccine primary series 6 months earlier or had J&J vaccine single dose 2 months earlier

Here is the data from CDC on the vaccine effectiveness against Covid based on epidemiologic data on emergency department (ED)/urgent care (UC) encounters or hospitalization during the recent Omicron-predominant period:2

 Vaccine effectiveness against ED/Urgent care encounters 

  • 2 doses of mRNA vaccine: 41% (69% <2 months vs 37% ≥5 months after last dose)
  • 3 doses of mRNA vaccine: 83% (87% < 2 months vs 66% 4 months vs 31% ≥5 months)

Vaccine effectiveness against hospitalization 

  • 2 doses of mRNA vaccine: 55% (71% < 2months vs 54% ≥5 months)
  • 3 doses of mRNA overall 88% (91% if < 2 months, 78% if ≥4 months)

So take full advantage of available Covid vaccines and maximize your chance of not getting Covid!

 

Bonus Pearl: Did you know that a recent CDC study found that people 18 years and older who received the same mRNA vaccine brand for all their vaccinations experienced fewer adverse reactions following the booster dose than they did after their second dose of mRNA vaccine, with 92% of reported reactions not considered serious?3

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References

  1. Covid-19 vaccine booster shots. Feb 2, 2022. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/booster-shot.html#:~:text=It%20depends.,after%20the%20J%26J%2FJanssen%20vaccine. Accessed Feb 24, 2022
  2. Waning 2-dose and 3-dose effectiveness of mRNA vaccines against Covid-19-associated emergency department and urgent care encounters and hospitalizations among adults during periods of delta and omicron variant predominance-VISION network, 110 states, August 2021-Jan 2022. Feb 18, 2022 https://www.cdc.gov/mmwr/volumes/71/wr/mm7107e2.htm#T1_down. Accessed Feb 24, 2022.
  3. New CDC studies: Covid-19 boosters remains safe, continue to offer high levels of protection against severe disease over time and during Omicron and delta waves. Feb 11, 2022. https://www.cdc.gov/media/releases/2022/s0211-covid-19-boosters.html. Accessed Feb 24, 2022

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Should healthy adults receive a Covid vaccine booster shot and why?

My middle-age immunocompromised patient receiving immunosuppressants has had 3 doses of mRNA Covid vaccine and is now 4 months out from her 3rd dose.  Should she consider a fourth dose of Covid vaccine?

FA Manian MD, MPH, , , , , , , , , , , , , Leave a comment

Yes! According to the Centers for Disease Control and Prevention (CDC) of the U.S.,1 persons who are “moderately or severely immunocompromised” and have received 3 doses of an mRNA vaccine (either Pfizer [12+ years old) or Moderna (18+ years old]) should receive a 4th dose (“booster”) at least 3 months after the 3rd dose.  Similarly, those who initially received a J&J vaccine followed by one of the aforementioned mRNA vaccines and are at least 2 months from the 2nd dose should also receive a 3rd dose (booster. 

The following are considered moderately or severely immunocompromised conditions by CDC: 

  • Active cancer treatment for tumors or cancers of the blood
  • Organ transplant with immunosuppressants on board
  • Stem cell transplant within the last 2 years or taking immunosuppressants
  • Moderate or severe primary immunodeficiency (eg, DiGeorge or Wiskott-Aldrich syndromes)
  • Advanced or untreated HIV infection
  • Active treatment with high-dose corticosteroids or other immunosuppressants

A published study2 of Covid-19-associated emergency department (ED) and urgent care (UC) encounters and hospitalization among adults during a period including Omicron variant predominance in 10 states found vaccine effectiveness for ED/UC visits dropping to 66% and for hospitalization to 78% by the 4th month after a 3rd dose (vs 87% and 91%, respectively during the 2 months after a 3rd dose).  This study did not distinguish immunocompromised from non-immunocompromised persons, however.  More data on the vaccine effectiveness in non-immunocompromised persons at high risk of Covid-19 related complications would be welcome.

Bonus Pearl: Did you know that of American adults who are fully vaccinated against Covid-19, only about 30% have received an additional Covid vaccine dose beyond the primary series ? 3 

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References

  1. Covid-19 vaccines for moderately or severely immunocompromised people (Updated Feb 17, 2022). Accessed Feb 21, 2022.  https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html?s_cid=10483:immunocompromised%20and%20covid%20vaccine:sem.ga:p:RG:GM:gen:PTN:FY21
  2. Waning 2-doe and 3-dose effectiveness of mRNA vaccines against Covid-10-associated emergency department and urgent care encounters and hospitalizations among adults during periods of delta and omicron variant predominance—Vision Network, 10 states, August 2021-January 2022. MMWR 2022; 71:255-63. https://www.cdc.gov/mmwr/volumes/71/wr/mm7107e2.htm?s_cid=mm7107e2_w
  3. Hubler S, Harman A. As Cov id surges, experts say U.S. booster effort is falling behind. NY Times, December 18, 2021. https://www.nytimes.com/2021/12/18/us/omicron-booster-shots-americans.html

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My middle-age immunocompromised patient receiving immunosuppressants has had 3 doses of mRNA Covid vaccine and is now 4 months out from her 3rd dose.  Should she consider a fourth dose of Covid vaccine?

Should patients with prior Covid receive Covid vaccine?

FA Manian MD, MPH, , , , , Leave a comment

Yes, as recommended by the CDC.  The weight of the evidence to date suggests that previously infected individuals should receive Covid vaccine to minimize their risk of acquiring Covid again for many reasons, including the following:

First, depending on the population and the variant of SARS-CoV-2 (the agent of Covid) studied, a significant proportion of infected individuals— from 5% to >35% based on some studies— fail to produce antibodies against SARS-CoV-2.1 In 1 study, lack of antibody production was associated with younger age, lower viral load and a trend toward milder symptoms.1

Second, the body of the evidence for infection-induced immunity is much more limited with less consistent findings than that for vaccine-induced immunity.2

Third, vaccination against Covid has been shown to enhance the immune response and reduce the risk of infection even in those with prior Covid.2 In fact, 1 study reported that the risk of reinfection is more than twice among those who were previously infected but not vaccinated compared to those who got vaccinated after having Covid.3  In another study, the risk of infection in adults was more than 5 times higher in unvaccinated but previously infected individuals compared to the vaccinated person who had not had an infection previously.4

Some authors5 who oppose routine vaccination of individuals previously infected with Covid have invoked a recent CDC study6 which showed that when Delta was the predominant strain, persons with prior Covid had lower rates of infection than persons who were vaccinated alone.  However, this study was performed when booster doses of Covid vaccine were not yet available to most people and before Omicron became the predominant variant. 

Bonus Pearl: Did you know that following Covid infection, neutralizing antibodies  have a biphasic decline with an initial half-life of 2-3 months followed by a slower decline thereafter?2

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References

  1. Liu W, Russell RM, Bibollet-Ruche F, et al. Predictors of nonseroconversion after SARS-CoV-2 infection. Emerg Infect Dis 2021;27:2454-58. Predictors of Nonseroconversion after SARS-CoV-2 Infection – Volume 27, Number 9—September 2021 – Emerging Infectious Diseases journal – CDC
  2. Science brief: SARS-CoV-2 infection-induced and vaccine-induced immunity. October 29, 2021. Science Brief: SARS-CoV-2 Infection-induced and Vaccine-induced Immunity | CDC
  3. Cavanaugh AM, Spicer KB, et al. Reduced risk of reinfection with SARS-CoV-2 after Covid-9 vaccination-Kentucky, may-June 2021. MMWR 2021;70:1081-83. Reduced Risk of Reinfection with SARS-CoV-2 After COVID-19 Vaccination – Kentucky, May-June 2021 – PubMed (nih.gov)
  4. Laboratory-confirmed Covid-19 among adults hospitalized with Covid-19-like illness with infection-induced or mRNA vaccine-induced SARS-CoV-2 immunity—Nine states, January-September 2021. MMWR 2021;70:1539-44. Laboratory-Confirmed COVID-19 Among Adults Hospitalized with COVID-19–Like Illness with Infection-Induced or mRNA Vaccine-Induced SARS-CoV-2 Immunity — Nine States, January–September 2021 | MMWR (cdc.gov)
  5. Makary M. The high cost of disparaging natural immunity to Covid. Wall Street Journal. January 26, 2022. The High Cost of Disparaging Natural Immunity to Covid – WSJ
  6. Leon Tm, Drabawila V, Nelson L, et al. Covid-19 cases and hospitalizations by Covid-19 vaccination status and previous Covid-19 diagnosis-California and New York, May -November 2021.  MMWR 2022;71:125-31 COVID-19 Cases and Hospitalizations by COVID-19 Vaccination Status and Previous COVID-19 Diagnosis — California and New York, May–November 2021 (cdc.gov)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Should patients with prior Covid receive Covid vaccine?