Influenza

Should I treat my patient with community-acquired pneumonia (CAP) with adjunctive corticosteroids?

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

It depends! You should consider ACs in immunocompetent patients with severe bacterial CAP in the absence of concurrent influenza, particularly in patients with a very high inflammatory response (eg, serum C-reactive protein [CRP] >150-200 mg/L). 1-13 In contrast, ACs is NOT recommended for patients with non-severe CAP.

Depending on the study, ACs in severe CAP has been associated with improvement in various patient outcomes, including reduced mortality, need for vasopressor or invasive mechanical ventilation, decrease in ICU stay and decrease in hospital length of stay.1-13 Significantly higher risk of hyperglycemia has been reported in the ACs group without demonstrable increase in the risk of upper GI bleed or hospital-acquired infections.2  

Which definition of severe CAP should we use when considering ACs? Unfortunately, it varies but a commonly cited definition is that proposed by the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA).9  When determining which patients may benefit from ACs, I favor a broader definition of severe CAP through modification of the ATS/IDSA criteria to include several other criteria used in major trials such as the seminal Community-Acquired Pneumonia Evaluation Corticosteroids (CAPE COD) study criteria and the Pneumonia Severity Index. 1-4   According to this “modified ATS/IDSA criteria”, severe CAP is likely in the presence of either one major criterion OR ≥3 minor criteria as detailed below.

Major criteria (1 needed):1. Septic shock with need for vasopressor; 2. Respiratory failure requiring invasive, non-invasive mechanical ventilation or high-flow nasal cannula; OR 3. Pneumonia severity index class IV or V.  Note: high-flow nasal cannula and PSI IV or V have been added to ATS/IDSA criteria

Minor criteria (3 needed):1. Respiratory rate ≥30/min; 2. Pa02/Fi02 ratio ≤250; 3. Multilobar infiltrates; 4. Confusion/disorientation; 5. BUN≥20 mg/dL; 6. Leukopenia (WBC<4,000/uL); 7. Thrombocytopenia (platelet count < 100,000/uL; 8. Hypothermia (core temp <96.8 ⁰ F, 36 ⁰ C); 9. Hypotension requiring aggressive fluid resuscitation.

In addition, a high inflammatory response based on CRP greater than 150-200 mg/L significantly increases the odds of a favorable outcome (eg, reduced mortality) in CAP when ACs is used.2,3,8 In fact, in a meta-analysis involving data-driven analysis of randomized trials, a significant reduction in mortality with ACs was observed only in those with CRP>204 mg/dL (6.1% vs 13%).8  In a subgroup analysis of CAPE COD study, mortality was significantly reduced only in patients with CRP>150 mg/L (risk difference -7.3 %).2  A 2015 study involving only patients with CRP>150 mg/L and meeting ATS/IDSA criteria for severe CAP or PSI class V, treatment failure (composite deterioration/invasive mechanical ventilation and death within 72 h) was significantly lower in the ACs group (13% vs 31%).3   

Collectively, in the absence of any contraindication to corticosteroids or concurrent influenza, the weight of the evidence supports ACs in select patients with severe CAP, particularly when associated with CRP>150 mg/L.  In contrast, for patients with non-severe CAP and presumed lower level of inflammation, the benefit of ACs may not outweigh its risks and is not recommended, unless there are other indications for their use (eg, COPD exacerbation).  For all other patients, including those without severe CAP but with high CRP levels as above or severe CAP with lower CRP levels, ACs should be considered on a case-by-case basis.

When indicated for severe CAP, based on the inclusion criteria used by various clinical trials, ACs should be started as soon as severe CAP is diagnosed, preferably within 24 h.2,13 As for the choice of ACs regimen, no study has proven the superiority of one particular regime vs others.1  The CAPE COD study used IV hydrocortisone 200 mg/day continuous infusion for 4-8 days with taper over total of 8-14 days.2 Some have suggested methylprednisolone 0.5 mg/kg IV q 12 h or “typical doses” of 40-80 mg/day IV methylprednisolone equivalent for 5-7 days.1,3 Yet others have suggested that hydrocortisone 100 mg IV or methylprednisolone 40 mg IV be given in the emergency department as an initial dose when severe CAP is diagnosed. 11 If IV hydrocortisone is selected, a pragmatic approach using 50 mg every 6 hours, similar to that suggested in the management of septic shock by the 2026 Guidelines by the Surviving Sepsis Campaign14 may also be reasonable.

 

Bonus Pearls:

  1. Did you know that despite ready availability of antibiotics, mortality from CAP in hospitalized patients remains high with nearly 50,000 people dying each year in the U.S. alone? top-pneumonia-facts.pdf
  2. Did you know that in addition to their immune modulating action, experimental studies have shown that corticosteroids may decrease global bacterial burden in lung tissue and lead to less extensive pneumonia in piglets15 and significant reduction in intracellular bacterial survival in human monocytes?16 Who would have guessed?  

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References

  1. Chaudhuri D, Nei AM, Rochwerg B, et al. 2024 Focused update: Guidelines on use of corticosteroids in sepsis, acute respiratory distress syndrome, and community-acquired pneumonia. Crit Care Med 2024;52:e129-33. 2024 Focused Update: Guidelines on Use of… : Critical Care Medicine 
  2. Dequin P.-F, Meziani J.-P, Quenot T, et al. Hydrocortisone in severe community-acquire pneumonia. N Engl J Med 2023; 388: 1931-41. Hydrocortisone in Severe Community-Acquired Pneumonia | New England Journal of Medicine 
  3. Torres A, Sibila O, Ferrer M, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: A randomized clinical trial. JAMA 2015;313:677-86 .Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial – PubMed
  4. Metlay JP, Waterer GW. Time to treat severe community-acquired pneumonia with steroids? N Engl J Med 2023; 388:2001-2. Time to Treat Severe Community-Acquired Pneumonia with Steroids? | New England Journal of Medicine
  5. Pitre Ty, Pauley E, Chaudhuri D, et al. Corticosteroids for adult patients hospitalized with non-viral community-acquired pneumonia: a systematic review and meta-analysis. Intensive Care Medicine 2025; 51:917-29. Corticosteroids for adult patients hospitalised with non-viral community-acquired pneumonia: a systematic review and meta-analysis | Intensive Care Medicine | Springer Nature Link
  6. Soumare A, Kapfer T, Botrel T, et al. Systemic corticosteroids, mortality, and infections in pneumonia and acute respiratory distress syndrome. Ann Intern Med 2026; 179L67-80. Systemic Corticosteroids, Mortality, and Infections in Pneumonia and Acute Respiratory Distress Syndrome : A Systematic Review and Meta-analysis – PubMed
  7. Keisham B, Duhan S, Bajaj D, et al. Steroid therapy in community-acquired pneumonia: an updated systematic review and meta-analysis. Heart & Lung 2026;79:102839. Steroid Therapy in Community-Acquired Pneumonia: An Updated Systematic Review and Meta-Analysis – PubMed
  8. Smit JM, Van Der Zee PA, Stoff SCM, et al. Predicting benefit from adjuvant therapy with corticosteroids in community-acquired pneumonia: a data-driven analysis of randomized trials. Lancet Resp Med 2025;13:221-33. Predicting benefit from adjuvant therapy with corticosteroids in community-acquired pneumonia: a data-driven analysis of randomised trials – The Lancet Respiratory Medicine. 
  9. Jones BE, Ramirez JA, Oren E, et al. Diagnosis and management of community-acquired pneumonia. Am J Resp Crit Care 2026;212:24. Jones BE, Ramirez JA, Oren E, et al. Diagnosis and management of community-acquired pneumonia. Am J Resp Crit Care 2026;212:24. – Search
  10. Reyes LF, Morris AC, Serrano-Mayorga C, et al. Community-acquired pneumonia. Lancet 2025;406:2371-88. Community-acquired pneumonia – The Lancet
  11. Long B, Gottlieb M. 2025 guideline updates for community-acquired pneumonia diagnosis and management. Am J Emerg Med 2026;107:16-20. 2025 guideline updates for community-acquired pneumonia diagnosis and management – EM consulte
  12. Confalonleri M, Urbino R, Potena A, et al. Hydrocortisone infusion for severe community-acquired pneumonia: A preliminary randomized study. Am J Respir Crit Care Med 2005;171:242-8. Hydrocortisone Infusion for Severe Community-acquired Pneumonia | American Journal of Respiratory and Critical Care Medicine | Oxford Academic
  13. Pirracchio R, Venkatesh B, Legrand M. Low-dose corticosteroids for critically ill adults with severe pulmonary infections: A review. JAMA 2024;332:318-328.jama_pirracchio_2024_rv_240011_1721328820.09305 give steroids.pdf
  14. Prescott HC, Antonelli M, Alhazzani W, et al. Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock 2026. Crit Care Med 2026;54:725-812. Surviving Sepsis Campaign: International… : Critical Care Medicine
  15. Sibila O, Luna CM, Agusti C, et al. Effects of glucocorticoids in ventilated piglets with severe pneumonia. Eur Respir J 2008;32:1037-46. Effects of glucocorticoids in ventilated piglets with severe pneumonia | European Respiratory Society
  16. Meduri GU, Kananagat S, Bronze M, et al. Effects of methylprednisolone on intracellular bacterial growth. Clin Diag Lab Immunol 2001;8:1156-63.Effects of Methylprednisolone on Intracellular Bacterial Growth – PMC

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!

Should I treat my patient with community-acquired pneumonia (CAP) with adjunctive corticosteroids?

Is it just my imagination or are Covid-19 cases going down as influenza cases are surging out of control during this flu season?

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

No, you are not imagining! Although during respiratory tract infection (RTI) season several viruses such as rhinovirus, respiratory syncytial virus (RSV) and coronavirus may cocirculate, influenza virus frequently outcompetes many RTI viruses, likely through a phenomenon called “viral interference.” 1-4

A negative viral interference is observed when a virus that has already infected a host makes that host resistant to infection by the second virus (isn’t that fascinating?). Although there a lot of virus, host and environmental variables that affect infection risk, potential mechanisms for this interference include a rapid and robust innate immune response to the first virus such as through upregulation of interferon (IFN) production which can protect against unrelated viruses, thereby creating a temporary “antiviral state.” 1-4

A negative viral interference has been shown between influenza-A virus (IAV) and SARS-CoV-2 by a cool 2024 study using the air-liquid interface culture model of the differentiated human airway epithelium. 4 Replicating IAV induced a robust interferon response and suppressed SARS-CoV-2 replication in both sequential and simultaneous infections. In contrast, SARS-CoV-2 did not demonstrate significant viral interference with IAV.  The researchers took their experiment a step further and found that oseltamivir (Tamiflu), an anti-IAV agent, restored SARS-CoV-2 replication with IAV coinfection by reducing induction of IFN!

One explanation for the inability of SARS-CoV-2 to interfere with the production of influenza virus is its slower induction of IFN stimulating genes likely due to its more effective mechanisms of antagonizing the IFN response with infected cells.4 Another explanation is that SARS-CoV-2 has a slower growth rate than IAV, making it more susceptible to being “outgunned” by faster growing viruses. Some strains of IAV may also cause more damage to the epithelial cells than SARS-CoV-2 thus reducing the number of host cells available for SARs-CoV-2 infection.2 Last, secreted IFNs (eg, IFN λ) can also bind to receptors present at the surface of infected and neighboring state blocking the second virus from infecting the host.1

So, it looks like competition among living forms in this world also applies to the world of viruses!

Bonus Pearl: Did you know that the concept of viral interference was first described in the 1960s following observation that oral administration of live enterovirus vaccines decreased detection of several unrelated respiratory viruses such as influenza virus, RSV and human adenovirus?1

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References

  1. Piret J, Bolvin G. Viral interference between respiratory viruses. Emerg Infect Dis 2022;28:273-280. Viral Interference between Respiratory Viruses – PubMed
  2. Gilbert-Girard S, Piret J, Carbonneau J, et al. Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses. PLOS Pathogens 2024;20(7):e1012017. Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses – PubMed
  3. Kaaijk P, Swaans N, Nicolaie AM, et al. Contribution of influenza viruses, other respiratory viruses and viral co-infections to influenza-like illness in older adults. Viruses 2022;14, 797. Contribution of Influenza Viruses, Other Respiratory Viruses and Viral Co-Infections to Influenza-like Illness in Older Adults – PubMed
  4. Cheemarla NR, Watkins TA, Mihaylova VT, et al. Viral interference during influenza A-SARS-CoV-2 coinfection of the human airway epithelium and reversal by oseltamivir. J Infect Dis 2024;229:1430-4. Viral Interference During Influenza A-SARS-CoV-2 Coinfection of the Human Airway Epithelium and Reversal by Oseltamivir – PubMed

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!

 

 

Is it just my imagination or are Covid-19 cases going down as influenza cases are surging out of control during this flu season?

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?

What’s the evidence that immunocompromised patients need a 3rd booster mRNA Covid vaccine shot?

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

At this time, the Centers for Disease Control and Prevention (CDC) recommendation for a booster shot of an mRNA vaccine in patients with moderate to severe immunocompromised state (1,2) is based primarily on the concern for waning immunity following the initial series—including a decline in neutralizing antibodies— in this patient population, and the finding that at least some immunocompromised patients may have a significant improvement in certain laboratory measurements of immunity following their booster shot. 

Although there are no randomized-controlled trials of the efficacy of the 3rd shot in protecting against Covid-19 in immunocompromised patients, the recent surge in the highly transmissible SARS-CoV-2 variants in many parts of the world (including the U.S.)  as well as immunocompromised patient population accounting for nearly one-half of all breakthrough Covid-19 cases requiring hospitalization (1) make it urgent to adopt these recommendations. 

A randomized trial involving 120 solid organ transplant patients (median age 67 y) found higher neutralizing antibody levels and SARS CoV-2 specific T-cell counts after the mRNA-1273 (Moderna) vaccine booster dose compared to placebo (3).

In another study involving 101 solid organ transplant patients, of 59 subjects who were seronegative before the 3rd dose, 44% became seropositive 4 weeks after the 3rd vaccine dose ( BNT162b2-Pfizer vaccine administered 2 months after the second dose). Patients who did not have an antibody response were older, had higher degree of immunosuppression and had a lower estimated glomerular filtration rate than those with antibody response (4).

A “spectacular increase” in anti-spike antibodies with levels close to the general population has also been reported among hemodialysis patients receiving a third dose of Pfizer mRNA vaccine (5). 

Until further data from larger studies become available,  these studies support administration of a 3rd dose booster mRNA vaccine in moderate to severely immunosuppressed individuals.

Bonus Pearl: Did you know that although immunocompromised patients have significantly worse influenza outcome, the data on the impact of immunocompromised status on the outcome of Covid-19 is less clear with published evidence that both supports and refutes this association (6)?  

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References

  1. CDC. Data and clinical considerations for additional doses in immunocompromised people: ACIP Meeting, July 22, 2021. ACIP Data and Clinical Considerations for Additional Doses in Immunocompromised People (cdc.gov)
  2. CDC. Interim clinical considerations for use of Covid-19 vaccines currently authorized in the United States. August 13, 2021. Interim Clinical Considerations for Use of COVID-19 Vaccines | CDC
  3. Hall VG, Ferreira VH, Ku T, et al. Randomized trial of a third dose of mRNA-1273 vaccine recipients. N Engl J Med 2021, Aug 11. Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients | NEJM
  4. Kamar N, Abravanel F, Marion O. Three doses of an mRNA Covid-19 vaccine in solid-organ transplant recipient. N Engl J Med 2021, Aug 12.Three Doses of an mRNA Covid-19 Vaccine in Solid-Organ Transplant Recipients | NEJM
  5. Frantzen L, Thibeaut S, Moussi-Frances J, et al. Covid-19 vaccination in haemodialysis patients: Good things come in threes… Neph Dial Transplant, 20 July 2023. COVID-19 Vaccination in Haemodialysis Patients: Good things come in threes… – PubMed (nih.gov)
  6. Parisi C. An opportunity to better understand the impact of coronavirus on immunocompromised patients. J Infect Dis 2021;224:372-3. Opportunity to Better Understand the Impact of Coronaviruses on Immunocompromised Patients | The Journal of Infectious Diseases | Oxford Academic (oup.com)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate 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 evidence that immunocompromised patients need a 3rd booster mRNA Covid vaccine shot?

My elderly patient developed a flare-up of her gout few days after receiving Covid-19 vaccine. Is there a connection between immunization and gout flare?

FA Manian MD, MPH, , , , , , , , , , , , , , , 1 Comment

Although the connection between Covid-19 vaccination and gout flare has yet to be established, higher rates of gout/gout flare following the administration of several other vaccines (eg, influenza, tetatnus, recombinant zoster) have been reported.1  Thus, it is conceivable that Covid-19 vaccine may also be associated with gout flare as more and more people are immunized.  

A 2019 prospective study of over 500 patients with gout found that vaccination was associated with 2-fold higher odds of gout flare (aO.R. 1.99; 95% ci 1.01-3.89) during the 2 day period following immunization; no information on the type of vaccines administered was provided, however.1  Similarly,  higher risk of gout (3.6-fold) has been reported in recipients of recombinant zoster vaccine following immunization.1

An intriguing mechanism explaining the association of vaccination and gout flare is the activation of the Nlrp3 inflammasome, a multiprotein complex produced in response to diverse stimuli such as uric acid crystals and ATP released from tissue injury/necrotic cells.2 Of interest, ~25% of patients with asymptomatic hyperuricemia have been found to have evidence of monosodium urate crystals in and around their joints by advanced imaging, such that vaccination may potentially bring out more inflammatory response and gout flare. 3 

Although aluminum adjuvants intended to increase the immunogenicity of one-half of all routine adult vaccines (eg, tetanus, diphteria, pertussis) have been shown to activate the Nlrp3 inflammasome in vitro, neither currently available mRNA vaccines (Pfizer, Moderna) nor the Johnson&Johnson vaccine contains aluminum as an adjuvant. 4  

Despite the potential for gout flare following adult vaccination, it should be emphasized that the absolute risk is still low and pales compared to the overwhelming benefits of vaccination in general.1

Bonus Pearl: Did you know that, in addition to the usual uric acid lowering drugs, losartan, fenofibrate and some non-steroidal anti-inflammatory drugs, such as indomethacin, also lower serum uric acid levels? 5,6

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References

  1. Yokose C, McCormick N, Chen C, et al. Risk of gout flares after vaccination: a prospective case-crossoverstudy. Ann Rheum Dis 2019;78:1601-1604. https://ard.bmj.com/content/early/2019/07/31/annrheumdis-2019-215724.info?versioned=true
  2. Lyer SS, Pulskens WP, Sadler JJ, et al. Necrotic cells trigger a sterile inflammatory response throught the Nlrp3 inflammasome. PNAS 2009;106:20388-20393. https://pubmed.ncbi.nlm.nih.gov/19918053/
  3. Yokose C, Choi H. Response to “Clarification regarding the statement of the association between the recombinant zoster vaccine (RZV) and gout flares’ by Didierlaurent etal. Ann Rheum Dis Month, December 2019. https://ard.bmj.com/content/annrheumdis/early/2019/12/18/annrheumdis-2019-216670.full.pdf
  4. Covid-19 vaccine information. https://covidvaccine.mo.gov/ Accessed March 16, 2021.
  5. Daskalopoulou SS, Tzovaras V, Mikhailidis DP, et al. Effect on serum uric acid levels of drugs prescribed for indications other than treating hyperuricaemia. Current Pharmaceutical Design 2005;11:4161-75. https://www.eurekaselect.com/60510/article
  6. Tiitinen S, Nissila M, Ruutsalo HM, et al. Effect of nonsteroidal anti-inflammatory drugs on the renal excretion of uric acid. Clin Rheumatol 1983;2:233-6. https://pubmed.ncbi.nlm.nih.gov/6678696/#:~:text=The%20effect%20of%209%20nonsteroidal,studied%20had%20no%20significant%20influence.

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 or its affiliate healthcare centers. 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 elderly patient developed a flare-up of her gout few days after receiving Covid-19 vaccine. Is there a connection between immunization and gout flare?

What’s the connection between Covid-19 and persistent fatigue?

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

Fatigue is one of the most common symptoms in patients with Covid-19, both during the acute illness as well during the weeks or months that follows it. Depending on the study, fatigue has been reported in around 30%-80% of patients at 2-3 weeks to 6 months or longer after the onset of illness (1-4).

In a study of hospitalized patients with Covid-19, ~80% of patients complained of fatigue during the acute illness, with ~50% having persistent fatigue at a mean follow-up of 60 days following onset of illness (1). Persistent fatigue was the most common symptom during the post-Covid-19 period, followed by dyspnea, joint pain, chest pain and cough.

In another study, 52.3% of patients with Covid-19 complained of persistent debilitating fatigue at a median of 10 weeks after initial onset of symptoms, despite a negative test for the virus (2). Of interest, there was no association between severity of Covid-19 illness/need for hospitalization and post-covid fatigue.  No association was found between routine laboratory markers of inflammation, WBC profile, LDH, C-reactive protein or interleukin-6 levels and persistent fatigue.

A CDC survey of outpatients with Covid-19 patients at 14-21 days from test date found persistent fatigue in one-third of patients (3).   

A MedRxive study (pending peer review) of over 3700 patients with definite (27%) or probable diagnosis of Covid-19 from 56 countries (>90% not hospitalized) reported fatigue in 78% of patients after 6 months (4).

Although the true nature or course of persistent fatigue following Covid-19 has yet to be clearly defined, In some respects, it’s reminiscent of chronic fatigue syndrome associated with many acute viral infections, such as SARS, EBV, and enteroviruses (5-7).

Bonus pearl: Did you know that persistent fatigue following Covid-19 may be more frequent than that following influenza in which >90% of outpatients recover within about 2 weeks (3)?

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References

  1. Carfi A, Bernabei R, Landi. Persistent symptoms in patients after acute COVID-19.JAMA 2020;324:603-605. https://pubmed.ncbi.nlm.nih.gov/32644129/
  2. Townsend L, Dyer AH, Jones K, et al. Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection. PLOS ONE 2020. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240784   
  3. Tenforde MW, Kim SS, Lindsell CJ, et al. Duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network—United States, March—June 2020. MMWR 2020;69:993-98. https://www.cdc.gov/mmwr/volumes/69/wr/mm6930e1.htm
  4. Davis HE, Assaf GS, MCorkell L, et al. Characterizing long COVID in an international cohort:7 months of symptoms and their impact. MedRxive 2020. https://www.medrxiv.org/content/10.1101/2020.12.24.20248802v2.full.pdf
  5. Chia JKS, Chia AY. Chronic fatigue syndrome is associated with chronic infection of the stomach. Clin Pathol 2008;61:43-48. https://jcp.bmj.com/content/61/1/43
  6. Moldofsky H, Patcai J. Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case control study. BMC Neurol 2011;11:37. https://pubmed.ncbi.nlm.nih.gov/21435231/
  7. Hickie I, Davenport T, Whitfield D, et al. Post-infective and chronic fatigue syndrome precipitated by pathogens: prospective cohort study. BMJ 2006;333:575. https://jcp.bmj.com/content/61/1/43

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital or its affiliated institutions. 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 connection between Covid-19 and persistent fatigue?

How can people with a respiratory virus such as Covid-19 be contagious even when they don’t cough or sneeze?

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

Couple of factors likely play a role in the transmission of respiratory viruses such as Covid-19 even in the absence of respiratory symptoms: 1. Generation of small droplets through everyday activities such as talking and breathing; 2. Presence of infectious virus in the respiratory tract before onset of symptoms.1-4

Small droplet generation during every day activity: Normal human speech and breathing can yield small particles or droplets that are too small to see by naked eye but are perfectly capable of serving as vehicles for aerial transport (more like hot air balloons than 737’s!) of a variety of communicable respiratory pathogens. 1  These small particles are believed to originate from the mucosal layers coating the respiratory tract as well as from vocal cord adduction and vibration within the larynx.1

In some cool experiments involving normal volunteers,1 the rate of particle emission during normal human speech positively correlated with the loudness of voice, ranging from 1-50 particles/second, irrespective of the language spoken (English, Spanish, Mandarin, or Arabic).  Perhaps, equally intriguing was identification of “speech superemitters”, consistently releasing an order of magnitude more particles than other participants.

Simply counting out loud has been associated with around 2-10 times as many total particles emitted as a single cough, 2 and the percentage of airborne droplet nuclei generated by singing is several times more than that emitted during normal talking and more like that of coughing! 3 Given, these observations, perhaps, the unfortunate outbreak of Covid-19 among members of a church choir in state of Washington 5 is not totally unexpected.

Presence of infectious virus in persons without symptoms:  An estimated 18% to 75% of patients testing positive for Covid-19 have no symptoms. This of course means that irrespective of whether symptoms ever develop, persons with Covid-19 may serve as a source of infection, by just breathing, talking, or singing when around susceptible people.

For these reasons, social distancing and wearing of masks during a pandemic makes sense!

Bonus Pearl: Did you know that infectious viral particles can be recovered from 40% of breath samples of patients with influenza? 6

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 References

  1. Asadi S, Wexler AS, Cappa CD, et al. Aerosol emission and superemission during human speech increase with voice loudness. Scientific Reports 2019;9:2348. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382806/
  2. Loudon RG, Roberts RM. Droplet expulsion from the respiratory tract. Am Rev Resp Dis 1967;435-42. https://doi.org/10.1164/arrd.1967.95.3.435
  3. Loudon RG, Roberts MR. Singing and the dissemination of tuberculosis. Am Rev Resp Dis 1968;98:297-300. DOI: 10.1164/arrd.1968.98.2.297 https://www.atsjournals.org/doi/abs/10.1164/arrd.1968.98.2.297?journalCode=arrd
  4. Lai KM, Bottomley C, McNerney. Propagation of respiratory aerosols by the Vuvuzela. PLoS One 2011;6:e20086. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100331/
  5. Read R. A choir decided to go ahead with rehearsal. Now dozens of members have COVID-19 and two are dead. Los Angeles Times March 29, 2020. https://www.latimes.com/world-nation/story/2020-03-29/coronavirus-choir-outbreak
  6. Yan J, Grantham M, Pantelic J, et al. Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community. PNAS 2018;115:1081-1086 https://www.pnas.org/content/115/5/1081

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its 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 can people with a respiratory virus such as Covid-19 be contagious even when they don’t cough or sneeze?

Does a positive routine PCR test for Covid-19 virus mean the person is infectious?

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

Not necessarily! Although a positive routine PCR test for Covid-19 indicates the presence of the virus in a clinical specimen, it does not mean that the virus is still viable or transmissible, particularly as the patient may be recovering from Covid-19. Viral cultures are often needed to help answer this question. 1-5

In a study of 9 hospitalized patients with Covid-19, no viable Covid-19 virus could be found by culture in any specimen beyond 8 days following onset of symptoms despite a positive routine PCR for up to 13 days. Successful growth of the virus was dependent in part on viral load, with samples containing <106 copies/mL never yielding any viable virus.1  

In the same study, none of stools that were positive for Covid-19 virus by PCR were positive by culture.  The authors concluded that there is “little residual risk of infectivity” beyond day 10 of symptoms when sputum contains less than 100,000 viral RNA copies /ml.  Of note, the patients in this study were young- to middle-aged without significant underlying disease and had milder disease, so the results may not necessarily be generalizable to other patients with Covid-19. 1

The discrepancy between a positive PCR and negative culture has been seen with other respiratory pathogens,  such as respiratory syncytial virus (RSV) and influenza. In a study involving experimentally infected subjects with RSV, the average duration of viral shedding was 9.2 days by PCR compared to 7.2 days by viral culture.2 In another study involving patients with symptomatic influenza, virus could be detected for up to 7 days with PCR compared to 1-2 days by viral culture.3

Factors that may explain this discrepancy include suboptimal sample transport, low viral titers,  and the presence of neutralizing antibody in the clinical specimen.2,3

So, despite our incomplete knowledge, don’t assume that PCR positivity means the presence of live virus capable of transmitting Covid-19!

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References

  1. Wolfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-19. Nature 2020; April 1. https://www.nature.com/articles/s41586-020-2196-x
  2. Falsey AR, Formica MA, Treanor JJ, et al. Comparison of quantitative reverse transcriptase-PCR to viral culture for assessment of respiratory syncytial virus shedding. J Clin Microbiol 2003;41:4160-65. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC193781/pdf/0106.pdf
  3. Van Elden LJR, Nijhuis M, Schipper P, et al . Simultaneous detection of influenza viruses A and B using real-time quantitative PCR. J Clin Microbiol 2001;39:196-200. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC87701/
  4. Cangelosi GA, Meschke JS. Dead or alive:molecular assessment of microbial viability. App Environ Microbiol 2014;80:5884-91.
  5. European Centre for Disease Prevention and Control. Novel coronavirus (SARS-CoV-2). https://www.ecdc.europa.eu/en/publications-data/novel-coronavirus-sars-cov-2-discharge-criteria-confirmed-covid-19-cases

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its 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!

 

Does a positive routine PCR test for Covid-19 virus mean the person is infectious?

What’s the evidence that people without symptoms can transmit Covid-19 to those around them?

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

Rapid spread of Covid-19 virus has been attributed in large part to its ease of transmission from person to person even before symptoms develop, particularly since an estimated 18% to 75% of patients testing positive for Covid-19 have no symptoms. 1-4

Transmission before onset of symptoms (presymptomatic): Modeled estimates for the percentage of transmissions that occur from presymptomatic patients range from 37% to as high as 62% based on studies of patients in the cities of Tianjin and Guangzhou in China, as well as Singapore.5-7 Infectiousness appears to begin within 1-3 days prior to symptoms.8-10

Transmission when symptoms never develop (asymptomatic): Asymptomatic transmission was invoked in a familial cluster in Anyang, China where 5 patients developed Covid-19 after a 6th asymptomatic family member returned home from Wuhan, China. The asymptomatic patient never developed symptoms—such as fever or respiratory symptom— and had a normal chest CT, but briefly tested positive for Covid-19 by RT-PCR before testing negative later.11

It’s important to point out that up to ~75% of patients who are initially “asymptomatic” later develop symptoms. 12-14 So what we often call “asymptomatic” may actually be “presymptomatic.”

Transmission of Covid-19 before onset of symptoms is in distinct contrast to SARS, another coronavirus disease, which was transmitted only when a person was symptomatic and was easier to control. This unique property among coronaviruses may be explained by the high tropism of Covid-19 virus not only for the lungs (as in case of SARS virus) but also for the upper respiratory tract.15,16 As such, Covid-19 behaves more like influenza viruses whose upper respiratory tract binding is thought to promote their rapid transmission even before symptoms develop.17  No wonder, Covid-19 spread like wild fire!

 

Coauthor, Bruce Tiu, Harvard Medical Student, Boston, MA

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References

 

  1. Mizumoto K, Kagaya K, Zarebski A, et al. Estimating the asymptomatic proportion of coronavirus diseae 2019 (COID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Euro Surveill.2020;25(10):pii=2000180 https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.10.2000180?ftag=MSF0951a18
  2. Kimaball, A, Hatfield KM, Arons M, et al. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility—King County, Washington, March 2020. MMWR 2020;69:377-381. https://www.cdc.gov/mmwr/volumes/69/wr/mm6913e1.htm
  3. Hu Z, Song C, Xu C, et al. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Sci China Life Sci 2020 Mar 4. https://www.ncbi.nlm.nih.gov/pubmed/32146694
  4. Day M. Covid-19: identifying and isolating asymptomatic people helped eliminate virus in Italian village. BMJ 2020;368 https://www.bmj.com/content/368/bmj.m1165
  5. He X, Lau E, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. medRxiv. https://www.medrxiv.org/content/10.1101/2020.03.15.20036707v2
  6. Ferretti L, Wymant C, Kendall M, et al. Quantifying SARS-CoV-2 transmission suggests epidemic control with digital contact tracing [published online ahead of print, 2020 Mar 31]. Science. 2020; eabb6936. https://science.sciencemag.org/content/early/2020/03/30/science.abb6936
  7. Ganyani T, Kremer C, Chen D, et al. Estimating the generation interval for COVID-19 based on symptom onset data. medRxiv. https://www.medrxiv.org/content/10.1101/2020.03.05.20031815v1
  8. Wei WE, Li ZB, Chiew CJ, et al. Presymptomatic transmission of SARS-CoV-2 — Singapore, January 23–March 16, 2020. MMWR Morb Mortal Wkly Rep. ePub: 1 April 2020. https://www.cdc.gov/mmwr/volumes/69/wr/mm6914e1.htm
  9. He X, Lau E, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. medRxiv. https://www.medrxiv.org/content/10.1101/2020.03.15.20036707v2
  10. Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N Engl J Med. 2020;382(10):970–971. https://www.nejm.org/doi/full/10.1056/NEJMc2001468
  11. Bai Y, Yao L, Wei T, et al. Presumed Asymptomatic Carrier Transmission of COVID-19 [published online ahead of print, 2020 Feb 21]. JAMA. 2020;e202565. https://jamanetwork.com/journals/jama/fullarticle/2762028
  12. Kimball A, Hatfield KM, Arons M, et al. Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility — King County, Washington, March 2020. MMWR Morb Mortal Wkly Rep. 2020;69:377–381 https://www.cdc.gov/mmwr/volumes/69/wr/mm6913e1.htm
  13. Chen, C. “What We Need to Understand About Asymptomatic Carriers if We’re Going to Beat Coronavirus”. ProPublica. 2020. https://www.propublica.org/article/what-we-need-to-understand-about-asymptomatic-carriers-if-were-going-to-beat-coronavirus
  14. WHO. Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). 2020. https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf
  15. Woelfel R, Corman VM, Guggemos W, et al. Clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster. medRxiv. https://www.medrxiv.org/content/10.1101/2020.03.05.20030502v1
  16. Peiris JS, Chu CM, Cheng VC, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003;361(9371):1767–1772. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(03)13412-5/fulltext
  17. van Riel D, den Bakker MA, Leijten LM, et al. Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses. Am J Pathol. 2010;176(4):1614–1618. https://wwwnc.cdc.gov/eid/article/26/6/20-0357_article

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its 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 evidence that people without symptoms can transmit Covid-19 to those around them?

Why might convalescent sera or plasma transfusion therapy be effective in the treatment of patients with Covid-19?

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

Of the myriad therapeutic approaches currently under consideration in our fight against Covid-19, convalescent sera/plasma therapy (CSPT) is particularly promising. The principle behind CSPT is to provide immediate immunity to susceptible people by administering the serum or plasma—therefore antibodies—of individuals who have successfully recovered from Covid-19.1

The theory behind using antibody-containing blood products to treat infections is by no means new and goes back to the 1890s when serum from exposed animals who recovered from disease was used to protect healthy animals against tetanus and diphtheria.2

Historically, CSPT has been used against poliomyelitis, measles, mumps, and influenza, and more recently in a smaller number of patients with SARS, H5N1 and H7N9 avian influenza and Ebola.1,3-8 A 2015 systematic review and exploratory meta-analysis of 32 studies involving severe acute respiratory infections of viral etiology (including influenza and SARS) found a reduction in mortality (odds ratio, 0.25, 95% C.I. 0.14-0.45), particularly when CSPT was administered early into the illness.3

Experience with 1918 Spanish influenza pandemic: A meta-analysis of 1703 hospitalized patients (Yes, scientists performed wonderful studies back then too despite a pandemic!) during the 1918 Spanish influenza pandemic demonstrated decreased mortality with administration of convalescent blood products with crude case-fatality rates dropping by one-half (16% vs 37% in controls)! Notably, patients who were treated within 4 days of pneumonia had one-third the case-fatality rate compared to those treated later.3

Experience with 2002-2004 SARS epidemic: A retrospective study from Hong Kong involving 80 patients with SARS (caused by another coronavirus, SARS-CoV-1) not responding to antibiotics/steroids/interferon but receiving CSPT reported a lower mortality rate with near significant (P=0.08) improvement in outcome and reduced mortality in the group that received CSPT before day 14 of the illness (6.3% vs 21.9%).4

What about Covid-19? A very preliminary report out of China involving 5 mechanically-ventilated patients with ARDS and rapid progression despite corticosteroids and antivirals found clinical improvement in all 5 patients. More specifically, body temperature normalized within 3 days in 4 of 5 patients and ARDS resolved in 4 patients at 12 days following transfusion, 2 patients were in stable condition and 3 patients were eventually discharged from the hospital.9

Of course, we should be mindful of potential adverse reactions due to CSP as well, such as allergic reactions, infections, transfusion-related acute lung injury (TRALI), and theoretical risk of antibody-dependent enhancement of infection (ADE).1 Only properly designed clinical studies can shed light on the safety and efficacy of CSPT in Covid-19.

Nevertheless, the historical data on the use of CSPT in serious viral infections is encouraging. In fact, the first US studies of CSPT in Covid-19 have already been approved by the FDA!10 Stay tuned!

Bonus pearl: Did you know that serum and plasma both refer to the noncellular fluid part of blood, but serum is collected after coagulation factors (fibrinogen) have been removed. Fortunately, both contain antibodies!

 

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Contributed by Bruce Tiu, Harvard Medical Student, Boston, MA.

References:

  1. Casadevall A, Pirofski L. The convalescent sera for containing COVID-19. J Clin Invest. 2020;130(4):1545-1548. doi: 10.1172/JCI138003 https://www.jci.org/articles/view/138003
  2. Eibl MM. History of immunoglobulin replacement. Immunol Allergy Clin North Am. 2008;28(4):737–viii. doi:10.1016/j.iac.2008.06.004 https://www.sciencedirect.com/science/article/abs/pii/S0889856108000702
  3. Mair-Jenkins J, Saavedra-Campos M, Baillie K, et al. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: A systematic review and exploratory meta-analysis. J Infect Dis 2015; 211: 80-90. https://academic.oup.com/jid/article/211/1/80/799341
  4. Luke TC, Kilbane EM, Jackson JL, et al. Meta-Analysis: Convalescent Blood Products for Spanish Influenza Pneumonia: A Future H5N1 Treatment?. Ann Intern Med. 2006;145:599–609. doi: 10.7326/0003-4819-145-8-200610170-00139 https://annals.org/aim/article-abstract/729754/meta-analysis-convalescent-blood-products-spanish-influenza-pneumonia-future-h5n1
  5. Cheng Y, Wong R, Soo YO, et al. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005;24(1):44–46. doi:10.1007/s10096-004-1271-9 https://link.springer.com/article/10.1007/s10096-004-1271-9
  6. Zhou B, Zhong N, Guan Y. Treatment with convalescent plasma for influenza A (H5N1) infection. N Engl J Med. 2007;357:1450–1. doi: 10.1056/NEJMc070359 https://www.nejm.org/doi/full/10.1056/NEJMc070359
  7. Chen L, Xiong J, Bao L, et al. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis 2020;20: 398-400. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30141-9/fulltext
  8. Wu XX, Gao HN, Wu HB, Peng XM, Ou HL, Li LJ. Successful treatment of avian-origin influenza A (H7N9) infection using convalescent plasma. Int J Infect Dis. 2015;41:3–5. doi: 10.1016/j.ijid.2015.10.009 https://www.ncbi.nlm.nih.gov/pubmed/26482389
  9. Shen C, Wang Z, Zhao F, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. Published online March 27, 2020. doi:10.1001/jama.2020.4783 https://jamanetwork.com/journals/jama/fullarticle/2763983
  10. https://thehill.com/regulation/healthcare/490768-first-us-coronavirus-patients-being-treated-with-plasma-therapy.

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its 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 might convalescent sera or plasma transfusion therapy be effective in the treatment of patients with Covid-19?